Differential bleaching susceptibility among coral taxa and colony sizes, relative to bleaching severity across Australia's Great Barrier Reef and Coral Sea Marine Parks.

Climate-induced coral bleaching represents the foremost threat to coral assemblages globally, however bleaching susceptibility varies among and within coral taxa. We compared bleaching susceptibility among 10 coral morpho-taxa and two colony size classes relative to reef-scale bleaching severity at 33 reefs across the Great Barrier Reef and Coral Sea Marine Parks in February-March 2020. Colony size and bleaching severity caused the hierarchy of bleaching susceptibility among taxa to change considerably. Notably, massive Porites shifted from being among the least likely taxa to exhibit bleaching, to among the most susceptible as overall bleaching severity increased. Juvenile corals (≤5 cm diameter) were generally more resistant to bleaching, except for Montipora and Pocillopora colonies, which were more likely to bleach than adults (>5 cm). These findings suggest that colony size and reef-scale bleaching severity are important determinants of bleaching susceptibility among taxa and provide insights into possible shifts in the structure of coral assemblages caused by bleaching events.

Effects of habitat fragmentation on the recruitment and early post-settlement survival of coral reef fishes.

The combined effects of global climate change and local anthropogenic stressors are leading to increasing loss and fragmentation of habitats. On coral reefs, habitat loss has been shown to influence the abundance and composition of associated fish assemblages, yet few studies have considered how habitat fragmentation may influence reef fish populations and assemblages. Herein, we compared survival, growth and recruitment of reef fish among experimental patches composed of six similar sized colonies of finely branching Pocillopora spp. but with different degrees of fragmentation: coral colonies were clumped (unfragmented), divided into two groups (low fragmentation), three groups (moderate fragmentation) or six groups (high fragmentation). Thirty settlement-stage Pomacentrus amboinensis were tagged, released onto each of the experimental patches, and their survival monitored daily for 11 days. Abundance and species richness of all reef fishes that subsequently recruited to the patches were also recorded, and used to analyse recruitment and community composition. There were no detectable differences among fragmentation treatments in the abundance or composition of reef fish assemblages that recruited to the patches, however, fragmentation influenced the survivorship of P. amboinensis. Highest survival of P. amboinensis was recorded on the unfragmented patches (61%.11 days-1) and highly fragmented habitat patches (54%.11 days-1) and lowest survival on low and moderate fragmentation treatments (47% and 48%.11 days-1, respectively). This suggests that there may be multiple competing processes that moderate mortality (e.g., predation) in unfragmented versus highly fragmented habitats, with moderate levels of habitat fragmentation having the greatest influence on the early post-settlement survival of corsal reef fish.

Coblation® intracapsular tonsillectomy (tonsillotomy) in children: A prospective study of 500 consecutive cases with long-term follow-up.

OBJECTIVES: Intracapsular tonsillectomy (tonsillotomy) has been used internationally, mainly in the management of obstructive sleep apnoea, rather than recurrent tonsillitis, with few published data evaluating its use for this latter indication. We present long-term prospective data from 500 paediatric cases undergoing Coblation® intracapsular tonsillectomy, for both obstructive and infective indications. DESIGN: Prospective case series, March 2013-January 2016, all with completed follow-up. SETTING: Tertiary paediatric otolaryngological practice. PARTICIPANTS: A total of 500 consecutive patients (6 months to 18 years, mean 5.1 years) undergoing Coblation® intracapsular tonsillectomy (with or without adenoidectomy), for obstructive and/ or infective indications, almost exclusively under the care of the senior author (DJT). MAIN OUTCOME MEASURES: Validated parent-reported T-14 tonsil symptom questionnaires were used in all cases pre- and postoperatively, including in the long term. Parents also recorded duration of analgesia, time to return to school, any complications and whether they would recommend the procedure. RESULTS: With a mean follow-up 7.4 months, symptom control has been excellent (mean total T-14 score (/70) 31.01 preoperatively, 2.68 postoperatively, P<.0000001), with similar trends for obstructive and infective domains. Two small secondary haemorrhages required readmission and observation only (0.4%); otherwise, no complications, delayed discharges or readmissions occurred; 12/500 (2.4%) have since undergone revision tonsil surgery, 10 for obstructive and 2 for infective symptoms, the majority in very young children, with revision adenoidectomy at the same time. More than 99% of parents would recommend the surgery. CONCLUSIONS: Our experience of this technique has been very positive, with excellent control of both obstructive and infective symptoms, and exceptionally low rates of complications. Further work will be required to allow conclusive demonstration of its advantages over extracapsular tonsillectomy.

Analysis of the incidence and factors predictive of inadvertent parathyroidectomy during thyroid surgery.

BACKGROUND: Inadvertent (or incidental) parathyroidectomy can occur during thyroidectomy. However, the factors associated with inadvertent parathyroidectomy remain unclear. This study aimed to report the rate of inadvertent parathyroidectomy during thyroidectomy and associated risk factors. METHODS: Variables including fine needle aspiration cytology findings, age, sex, thyroid weight, concurrent neck dissection, extent of thyroidectomy, and the presence of cancer and parathyroid tissue within the specimen were recorded for 266 patients. The incidence of post-operative hypocalcaemia was also recorded. Univariate and multivariate analysis were performed to identify factors associated with inadvertent parathyroidectomy. RESULTS: The inadvertent parathyroidectomy rate was 16 per cent. Univariate analysis revealed that cancer and concurrent neck dissection predicted inadvertent parathyroidectomy. On multivariate analysis, only concurrent neck dissection remained an independent predictor of inadvertent parathyroidectomy: it was associated with a fourfold increase in inadvertent parathyroidectomy. CONCLUSION: The inadvertent parathyroidectomy rate was 16 per cent and concurrent neck dissection was identified as an independent predictor of inadvertent parathyroidectomy.

Ecomorphological convergence in planktivorous surgeonfishes.

Morphological convergence plays a central role in the study of evolution. Often induced by shared ecological specialization, homoplasy hints at underlying selective pressures and adaptive constraints that deterministically shape the diversification of life. Although midwater zooplanktivory has arisen in adult surgeonfishes (family Acanthuridae) at least four independent times, it represents a clearly specialized state, requiring the capacity to swiftly swim in midwater locating and sucking small prey items. Whereas this diet has commonly been associated with specific functional adaptations in fishes, acanthurids present an interesting case study as all nonplanktivorous species feed by grazing on benthic algae and detritus, requiring a vastly different functional morphology that emphasizes biting behaviours. We examined the feeding morphology in 30 acanthurid species and, combined with a pre-existing phylogenetic tree, compared the fit of evolutionary models across two diet regimes: zooplanktivores and nonzooplanktivorous grazers. Accounting for phylogenetic relationships, the best-fitting model indicates that zooplanktivorous species are converging on a separate adaptive peak from their grazing relatives. Driving this bimodal landscape, zooplanktivorous acanthurids tend to develop a slender body, reduced facial features, smaller teeth and weakened jaw adductor muscles. However, despite these phenotypic changes, model fitting suggests that lineages have not yet reached the adaptive peak associated with plankton feeding even though some transitions appear to be over 10 million years old. These findings demonstrate that the selective demands of pelagic feeding promote repeated - albeit very gradual - ecomorphological convergence within surgeonfishes, while allowing local divergences between closely related species, contributing to the overall diversity of the clade.

Large predatory coral trout species unlikely to meet increasing energetic demands in a warming ocean.

Increased ocean temperature due to climate change is raising metabolic demands and energy requirements of marine ectotherms. If productivity of marine systems and fisheries are to persist, individual species must compensate for this demand through increasing energy acquisition or decreasing energy expenditure. Here we reveal that the most important coral reef fishery species in the Indo-west Pacific, the large predatory coral trout Plectropomus leopardus (Serranidae), can behaviourally adjust food intake to maintain body-condition under elevated temperatures, and acclimate over time to consume larger meals. However, these increased energetic demands are unlikely to be met by adequate production at lower trophic levels, as smaller prey species are often the first to decline in response to climate-induced loss of live coral and structural complexity. Consequently, ubiquitous increases in energy consumption due to climate change will increase top-down competition for a dwindling biomass of prey, potentially distorting entire food webs and associated fisheries.

Increasing ocean temperatures reduce activity patterns of a large commercially important coral reef fish.

Large-bodied fish are critical for sustaining coral reef fisheries, but little is known about the vulnerability of these fish to global warming. This study examined the effects of elevated temperatures on the movement and activity patterns of the common coral trout Plectropomus leopardus (Serranidae), which is an important fishery species in tropical Australia and throughout the Indo West-Pacific. Adult fish were collected from two locations on Australia's Great Barrier Reef (23°S and 14°S) and maintained at one of four temperatures (24, 27, 30, 33 °C). Following >4 weeks acclimation, the spontaneous swimming speeds and activity patterns of individuals were recorded over a period of 12 days. At 24-27 °C, spontaneous swimming speeds of common coral trout were 0.43-0.45 body lengths per second (bls(-1)), but dropped sharply to 0.29 bls(-1) at 30 °C and 0.25 bls(-1) at 33 °C. Concurrently, individuals spent 9.3-10.6% of their time resting motionless on the bottom at 24-27 °C, but this behaviour increased to 14.0% at 30 °C and 20.0% of the time at 33 °C (mean ± SE). The impact of temperature was greatest for smaller individuals (<45 cm TL), showing significant changes to swimming speeds across every temperature tested, while medium (45-55 cm TL) and large individuals (>55 cm TL) were first affected by 30 °C and 33 °C, respectively. Importantly, there was some indication that populations can adapt to elevated temperature if presented with adequate time, as the high-latitude population decreased significantly in swimming speeds at both 30 °C and 33 °C, while the low-latitude population only showed significant reductions at 33 °C. Given that movement and activity patterns of large mobile species are directly related to prey encounter rates, ability to capture prey and avoid predators, any reductions in activity patterns are likely to reduce overall foraging and energy intake, limit the energy available for growth and reproduction, and affect the fitness and survival of individuals and populations.

Bifocal optic and facial nerve t-cell lymphoma.

PURPOSE: Optic nerve and optic nerve sheath infiltration by a systemic lymphoma is uncommon, but is exceedingly rare when caused by a T-cell lymphoma. This then generally occurs in association with central nervous system (CNS) involvement. We report on a rare case of optic and facial nerve T-cell lymphoma infiltration, without CNS involvement. METHODS: A 63-year old female with systemic T-cell lymphoma in clinical remission presented with painful loss of vision in the left eye. She was initially treated for presumed recurrent optic neuritis. A thorough clinical work-up was performed, followed by an optic nerve biopsy with histopathology. RESULTS: There was no perception of light in the left eye, with a marked relative afferent pupillary defect. Fundoscopy showed significant optic disc oedema and a large peripapillary subretinal infiltration. Subsequently, she developed a 7th cranial nerve paresis. Cranial MRI showed thickening and contrast enhancement of the left optic nerve and right facial nerve. Optic nerve biopsy showed infiltration of CD3- and CD5- positive lymphocytes. A complete systemic workup revealed no evidence of disease elsewhere. The patient was thus considered to have bifocal cranial recurrence of T-cell lymphoma, for which radiotherapy was started. CONCLUSIONS: Optic nerve infiltration from systemic lymphoma is rare and generally occurs with CNS involvement. A bifocal pattern of recurrence from systemic T-cell lymphoma involving the right facial nerve and left optic nerve was seen in this patient. A review of the literature highlights the highly atypical nature of this presentation.

Crucial knowledge gaps in current understanding of climate change impacts on coral reef fishes.

Expert opinion was canvassed to identify crucial knowledge gaps in current understanding of climate change impacts on coral reef fishes. Scientists that had published three or more papers on the effects of climate and environmental factors on reef fishes were invited to submit five questions that, if addressed, would improve our understanding of climate change effects on coral reef fishes. Thirty-three scientists provided 155 questions, and 32 scientists scored these questions in terms of: (i) identifying a knowledge gap, (ii) achievability, (iii) applicability to a broad spectrum of species and reef habitats, and (iv) priority. Forty-two per cent of the questions related to habitat associations and community dynamics of fish, reflecting the established effects and immediate concern relating to climate-induced coral loss and habitat degradation. However, there were also questions on fish demographics, physiology, behaviour and management, all of which could be potentially affected by climate change. Irrespective of their individual expertise and background, scientists scored questions from different topics similarly, suggesting limited bias and recognition of a need for greater interdisciplinary and collaborative research. Presented here are the 53 highest-scoring unique questions. These questions should act as a guide for future research, providing a basis for better assessment and management of climate change impacts on coral reefs and associated fish communities.

Functional versatility supports coral reef biodiversity.

We explore the role of specialization in supporting species coexistence in high-diversity ecosystems. Using a novel ordination-based method to quantify specialist and generalist feeding structures and diets we examined the relationship between morphology and diet in 120 wrasses and parrotfishes from the Great Barrier Reef. We find that wrasses, despite their morphological diversity, exhibit weak links between morphology and diet and that specialist morphologies do not necessarily equate to specialized diets. The dominant pattern shows extensive overlap in morphology (functional morphospace occupation) among trophic groups; fish with a given morphology may have a number of feeding modes. Such trophic versatility may lay the foundation for both the origins and maintenance of high biodiversity on coral reefs.

Age- and sex-associated changes in cardiac beta(1)-adrenoceptors from the muscular dystrophy (mdx) mouse.

Variations in beta(1)-adrenoceptor function due to age or sex were examined in the mouse model of Duchenne muscular dystrophy. Positive chronotropic and inotropic responses to (-)-isoprenaline and antagonist effects of CGP20712A were determined in isolated right and left atria from young (12 week) and old (12 month) male and old (12 month) female mdx mice and their age- and sex-matched C57BL/10ScSn (C57) mice. There was no difference in efficacy to (-)-isoprenaline when expressed as an increase in the rate of contraction or force of contraction as a percentage of Ca(2+)-induced increase respectively in right or left atria from age- and sex-matched mdx and C57. Old mdx males showed a decreased sensitivity to (-)-isoprenaline (P<0.05) and a reduced affinity to CGP 20712A (P<0.05) in both right and left atria compared with old C57 males. These same changes were also observed in left atria between old and young mdx males. A reduced efficacy to (-)-isoprenaline was also evident when young and old mdx males were compared. In contrast, in old females, mdx showed an increased affinity to CGP20712A in left and right atria (P<0.05), and an enhanced sensitivity to (-)-isoprenaline in right atria. Finally, in left atria, the maximum Ca(2+)-induced increase in force of contraction was lower in all mdx compared to their age- and sex-matched C57 (P<0.05). In conclusion, age- and sex-associated changes in beta(1)-adrenoceptor function and responses to calcium were demonstrated in cardiac muscle from mdx mice, with a marked deterioration in beta(1)-adrenoceptor function occurring with aging in male mdx being particularly evident.

Changes in function of cardiac receptors mediating the effects of the autonomic nervous system in the muscular dystrophy (MDX) mouse.

Adrenergic and muscarinic receptor mediated effects on the force of contraction and heart rate were studied in the isolated left atria and right atria from dystrophin-deficient mdx mice and age matched C57BL/10ScSn (C57) mice, respectively. The pD(2) and pA(2) values of (-)-isoprenaline and CGP 20712A, respectively, were not different in left atria and right atria from mdx and C57 mice. (-)-Phenylephrine produced a small positive inotropic effect on mdx left atria that could be antagonized by prazosin, whereas in C57 left atria no positive inotropic response was seen. In contrast, the positive chronotropic effect of (-)-phenylephrine was reduced in right atria from mdx compared to C57 right atria (P<0.05). The potency and efficacy to carbachol in the presence of (-)-isoprenaline were higher in right atria from mdx compared to C57 mice (P<0.05), although in left atria only a greater efficacy was evident in mdx mice. In left atria, basal force of contraction and maximum Ca(2+)-induced increases in force of contraction were lower from mdx compared to C57 mice (P<0. 001 and P<0.05, respectively). In conclusion, marked changes were demonstrated in the function of alpha1-adrenoceptors and muscarinic receptors, but not in beta1-adrenoceptors in left and right atria from mdx mice.

Functional activity of antibodies at the bovine beta2-adrenoceptor.

Antibodies that can activate beta2-adrenoceptors (beta2-AR) have the potential to mimic the anabolic effects of beta-agonist drugs, such as clenbuterol. In this study, antibodies were raised in rabbits against two peptide analogues of the human beta2-adrenoceptor (beta2-AR): One peptide corresponded to the complete second outer loop of the receptor (24 amino acids; H24T), and the second peptide was a truncated version of the first (13 amino acids; H13C). Following affinity purification, the antibodies were screened to detect interaction with beta2-AR in vitro. Membrane proteins from transformed Escherichia coli that express the beta2-AR were separated using SDS PAGE and transferred to nitrocellulose sheets. Immunoblotting revealed a single protein band (39,000 Da) that was recognized by the affinity-purified anti-H24T antibodies. However, the anti-H13C antibodies did not recognize any protein bands in immunoblots. In ligand binding studies, anti-H24T antibodies at a concentration of 50 nM, increased the affinity (KD) of the radiolabeled antagonist [125I]iodocyanopindolol for the bovine beta2-AR from 31.7 pM to 25.3 pM (P < .05) without changing the receptor number. Anti-H13C antibodies had no effect on ligand binding. In competitive ligand binding experiments, there was no effect of antibodies on the affinity of bovine beta2-AR for the agonist (-)-isoproterenol. However, functional activity of anti-H24T antibodies was demonstrated in an organ bath study. The presence of antibodies caused a leftward shift in the concentration-response curve for (-)-isoproterenol-induced relaxation of isolated bovine smooth muscle strips. Values for pD2 (-log EC50) were reduced in the presence of 10 nM antibody (8.62 +/- .11) compared to controls (8.30 +/- .08; P < .05). Anti-H13C antibodies had no effect on (-)-isoproterenol-induced smooth muscle relaxation. These studies have demonstrated recognition, interaction, and functional activity of site-directed antibodies at the beta2-AR. Further studies will determine whether antibodies that potentiate activity at the beta2-AR may be evoked by the active immunization of cattle with the peptide H24T, and if so, whether this will cause the repartitioning of nutrients in a manner analogous to conventional beta2-agonists and thus provide an alternative to the use of xenobiotic compounds.

Characteristics of cyanopindolol analogues active at the beta 3-adrenoceptor in rat ileum.

1. Cyanopindolol (CYP) is a potent antagonist at the beta 3-adrenoceptor in rat ileum. Several analogues of CYP and pindolol were synthesized that also produced antagonist effects at the beta 3-adrenoceptor. However, at high concentrations, these compounds appear to act as "partial agonists'. This study was conducted to determine the structural requirements of CYP analogues necessary for antagonist activity and to examine the possibility that the agonist effects of CYP and its analogues may occur through a mechanism independent of beta-adrenoceptor activation. 2. Analogues of CYP and pindolol were tested for antagonist activity in rat ileum in which the beta 1- and beta 2-adrenoceptors were blocked. Fourteen compounds were tested against (-)-isoprenaline, and four of the more potent analogues were then tested against BRL 37344. The two most potent antagonists were CYP and iodocyanopindolol. The pKb values (negative log of equilibrium dissociation constant) obtained against (-)-isoprenaline were significantly higher than those obtained against BRL 37344, but the cause of this difference is not known. 3. Several structural requirements were determined for antagonist activity. Modification at the carbon atom alpha to the secondary amine caused the antagonist potency to fall as the level of saturation was reduced. Thus, a quaternary carbon group, such as t-butyl, produced the most potent antagonist. Substitution with a large moiety such as a cyclohexyl or benzyl group reduced antagonist activity, probably due to steric hindrance. Inclusion of an electron-withdrawing group, such as a cyano or ethylester moiety, alpha to the indole nitrogen, also increased the potency. Iodination of CYP and ethylesterpindolol at the 3-position of the indole ring did not increase antagonist potency. In contrast, iodination of the almost inactive analogues produced a significant increase in potency, suggesting that a beneficial electronic effect on the indole ring imparted by the iodo moiety may be able to offset partially the negative effects caused by either the steric hindrance, of lack of a quaternary carbon alpha to the secondary amine. 4. Values for pseudo-pD2 were also determined by conducting cumulative concentration-response studies up to the limit of drug solubility. For nine of the compounds tested, the pKb was significantly higher than the pseudo-pD2 value. 5. The discrepancy between the pKb and pseudo-pD2 values was examined further. The agonist effects of iodocyanopindolol, the agonist with the highest potency, were not antagonized by CYP which was the most potent antagonist of (-)-isoprenaline and BRL 37344 at the beta 3-adrenoceptor. This suggests that the agonist effects of iodoCYP were produced through a different mechanism: either via another receptor, another isoform of the rat beta 3-adrenoceptor, or through a non-receptor-mediated effect. Pseudo-pD2 values did not correlate with log P values for these compounds, indicating that their relaxant effects were not simply a function of their lipid solubility. 6. This study has highlighted several structural requirements for antagonist binding potency at the rat ileum beta 3-adrenoceptor and should assist in the development of potent selective antagonists for this receptor.

Atypical responses of rat ileum to pindolol, cyanopindolol and iodocyanopindolol.

1. Pindolol, cyanopindolol (CYP) and iodocyanopindolol (IodoCYP) have been reported to act either as antagonists, agonists or partial agonists at the beta 3-adrenoceptor in different preparations. A comprehensive investigation has not yet been described with these compounds tested in one tissue from one species. This study was conducted to delineate the pharmacological effects of pindolol, CYP and IodoCYP and to provide data on their affinities at the predominant beta-adrenoceptor in rat ileum. 2. The beta-adrenoceptors present in rat ileum were characterized in the presence of CGP 20712A and ICI 118 551, atropine and corticosterone, with (-)-isoprenaline used as an agonist. The role of the beta 1 and beta 2-adrenoceptors was determined by the omission of either CGP 20712A, ICI 118 551, or both, from the buffers. Conversely, the effectiveness of the beta 1- and beta 2-adrenoceptor blockade was examined by use of the beta 1-adrenoceptor-selective agonist, RO 363 and the beta 2-adrenoceptor-selective agonist, salbutamol. 3. There was no evidence for the presence of functional beta 1-adrenoceptors, and no strong evidence that beta 2-adrenoceptor stimulation contributed to the relaxant effects of (-)-isoprenaline. (-)-Phenylephrine did not produce relaxation of the tissue and 5-hydroxytryptamine produced contraction. 4. The beta 3-adrenoceptor-selective agonist, BRL 37344 and (-)-isoprenaline were potent full agonists (pD2 8.35 +/- 0.04 and 7.76 +/- 0.14 respectively), whereas ICI D7114 was less potent (pseudo pD2 6.92 +/- 0.15). These results indicate that the predominant functional beta-adrenoceptors in rat ileum are beta 3-adrenoceptors. 5. Partial agonist effects were produced by CYP (pD2 5.28 +/- 0.26) and IodoCYP (pD2 7.0 +/- 0.26), but not pindolol. All three compounds antagonized the effects of (-)-isoprenaline with pKb values of 6.68 +/- 0.10, 7.59 +/- 0.07 and 7.59 +/- 0.11 for pindolol, CYP and IodoCYP respectively. Likewise, CYP and IodoCYP antagonized the effects of BRL 37344 with pKb values of 7.20 +/- 0.22 and 7.21 +/- 0.14 respectively. This study provides the first functional data on the effects of IodoCYP, the ligand with the highest known affinity for the beta 3-adrenoceptor, at the characterized rat ileum beta 3-adrenoceptor. 6. In conclusion, whereas pKb values suggest that CYP and IodoCYP have a similar affinity for the beta 3-adrenoceptor in rat ileum, the higher potency of IodoCYP suggests that it promotes a greater coupling efficiency, or that its partial agonist effects are produced through a site other than the beta 3-adrenoceptor. The similar pKb values for CYP and IodoCYP at the beta 3-adrenoceptor contrast with their order of known affinities at the beta 1- and beta 2-adrenoceptors, where IodoCYP is far more potent than CYP. This provides evidence of further differences in the characteristics of the beta 3-adrenoceptors compared to the beta 1- and beta 2-adrenoceptors. Finally, the utility of IodoCYP as a beta 3-adrenoceptor antagonist would appear to be limited because of the greater magnitude of partial agonist effects that it produces.

Comparison of topical cyclosporin and dexamethasone for the treatment of chronic superficial keratitis in dogs.

Thirty dogs with chronic superficial keratitis (CSK) were randomly assigned to treatment with 0.2 per cent cyclosporin ointment or 0.1 per cent dexamethasone drops. They were treated for six weeks and examined before and after three and six weeks of treatment, and then every three weeks without treatment until the lesions recurred. The regression of the disease during the treatment and the time to a recurrence after the cessation of treatment were determined. Changes in the size of the corneal lesions were measured by image analysis of photographs taken at each examination, and the severity of adnexal changes such as conjunctival hyperaemia was assessed by means of a scoring system. Clinical evaluations suggested that both drugs were equally effective as treatments for CSK and a statistical analysis showed that they had reduced the size of the lesions to the same extent at each examination. There was a significant increase in tear production, measured by the Schirmer tear test, during the treatment with cyclosporin.

Beta 2-adrenoceptor densities do not correlate with growth, carcass quality, or meat quality in cattle.

Drugs that activate beta 2-adrenoceptors (beta-agonists) are known to have profound effects on growth, body composition, and meat quality. Physiologically, these adrenoceptors are activated and regulated by the hormone adrenaline. Because the response to a drug or hormone is dependent partly on the density of the tissue receptors, the potential for predicting growth, carcass quality, or meat quality from knowing beta 2-adrenoceptor density in three disparate sample sites in cattle was examined. Cell membrane fragments were prepared using samples of longissimus muscle, semitendinosus muscle, or ear obtained within 30 min of death from 48 steers. Beta 2-Adrenoceptor density (Bmax) was measured in these membrane preparations by saturating them with the radioligand [125I]iodocyanopindolol. There was no correlation between Bmax values measured in ear samples, longissimus muscles, or semitendinosus muscles. Bmax measured in samples of ear did not correlate with any growth or carcass traits, including weight gain, carcass weight, fat depth, or eye muscle area. Bmax measured in longissimus muscle only correlated weakly with meat color, and Bmax measured in semitendinosus muscle only correlated with carcass weight. We conclude that beta 2-adrenoceptor density is not a useful predictor of growth, carcass quality, or meat quality in cattle.

Positive inotropic responses of the sodium channel modulator BDF 9148 in diseased rat myocardium.

1. This study has defined the positive inotropic responses to the sodium channel modulator BDF 9148 in rats with hypertension, thyroid dysfunction, diabetes or dwarfism. Concentration-response curves to BDF 9148 and calcium chloride were determined in isolated left atria and left ventricular papillary muscles. 2. BDF 9148 increased force of contraction in left ventricular papillary muscles in all disease states with maximal responses comparable to calcium chloride. BDF 9148 potency was significantly decreased in muscles from diabetic rats only. 3. BDF 9148 produced similar responses in left atria except from hyperthyroid rats where negative inotropic responses only were measured. This exception confirms that the left atria is an imperfect model for ventricular responsiveness. 4. Thus, the increase in force of contraction in the ventricles as a consequence of sodium channel modulation by BDF 9148 is maintained in these disease states unlike responses to alpha-or beta-adrenoceptor agonists.

Cardiovascular effects of clenbuterol are beta 2-adrenoceptor-mediated in steers.

The mechanism through which the repartitioning agent clenbuterol increases heart rate was investigated. First, the relative importance of the beta 1- and beta 2-adrenoceptors was established in rat and bovine right atria in vitro. The positive chronotropic and inotropic effects of (+/-)isoproterenol in rat and bovine right atria, respectively, were markedly antagonized (P < .001) by the beta 1-adrenoceptor antagonist CGP 20712A but were antagonized less by the beta 2-adrenoceptor antagonist ICI 118 551 in rat (P < .01), but not in bovine atria, indicating a major role of the beta 1-adrenoceptors. Clenbuterol was only a partial agonist in rat right atria, increasing heart rate at high concentrations through stimulation of beta 1-adrenoceptors. In studies in vivo, clenbuterol decreased the plasma potassium concentration (P < .05) and increased the plasma glucose concentration (P < .05). Clenbuterol also reduced diastolic blood pressure (P < .01) and increased heart rate (P < .001). The increase in heart rate was not due to direct stimulation of cardiac beta 1-adrenoceptors by clenbuterol but was consistent with a reflex response to beta 2-adrenoceptor-mediated hypotension. This would have caused the activation of baroreceptors, which in turn would have resulted in both the release of norepinephrine to stimulate cardiac beta 1-adrenoceptors and the inhibition of cholinergic input to the heart. Thus, the effects of clenbuterol could be eliminated completely by ICI 118 551 or reduced by approximately 50% using CGP 20712A. The combination of treatment of clenbuterol and CGP 20712A could be useful. It may allow the full repartitioning effects seen with the beta 2-agonist alone, but with a markedly attenuated effect on the heart. Such a treatment regimen may also help reduce the increased energy expenditure and loss of appetite seen following the initial administration of clenbuterol.