Early Cenozoic Decoupling of Climate and Carbonate Compensation Depth Trends.

Our understanding of the long-term evolution of the Earth system is based on the assumption that terrestrial weathering rates should respond to, and hence help regulate, atmospheric CO2 and climate. Increased terrestrial weathering requires increased carbonate accumulation in marine sediments, which in turn is expected to result in a long-term deepening of the carbonate compensation depth (CCD). Here, we critically assess this long-term relationship between climate and carbon cycling. We generate a record of marine deep-sea carbonate abundance from selected late Paleocene through early Eocene time slices to reconstruct the position of the CCD. Although our data set allows for a modest CCD deepening, we find no statistically significant change in the CCD despite >3 °C global warming, highlighting the need for additional deep-sea constraints on carbonate accumulation. Using an Earth system model, we show that the impact of warming and increased weathering on the CCD can be obscured by the opposing influences of ocean circulation patterns and sedimentary respiration of organic matter. From our data synthesis and modeling, we suggest that observations of warming, declining δ13C and a relatively stable CCD can be broadly reproduced by mid-Paleogene increases in volcanic CO2 outgassing and weathering. However, remaining data-model discrepancies hint at missing processes in our model, most likely involving the preservation and burial of organic carbon. Our finding of a decoupling between the CCD and global marine carbonate burial rates means that considerable care is needed in attempting to use the CCD to directly gauge global carbonate burial rates and hence weathering rates.

Impact of high CO2 on the geochemistry of the coralline algae Lithothamnion glaciale.

Coralline algae are a significant component of the benthic ecosystem. Their ability to withstand physical stresses in high energy environments relies on their skeletal structure which is composed of high Mg-calcite. High Mg-calcite is, however, the most soluble form of calcium carbonate and therefore potentially vulnerable to the change in carbonate chemistry resulting from the absorption of anthropogenic CO2 by the ocean. We examine the geochemistry of the cold water coralline alga Lithothamnion glaciale grown under predicted future (year 2050) high pCO2 (589 µatm) using Electron microprobe and NanoSIMS analysis. In the natural and control material, higher Mg calcite forms clear concentric bands around the algal cells. As expected, summer growth has a higher Mg content compared to the winter growth. In contrast, under elevated CO2 no banding of Mg is recognisable and overall Mg concentrations are lower. This reduction in Mg in the carbonate undermines the accuracy of the Mg/Ca ratio as proxy for past temperatures in time intervals with significantly different carbonate chemistry. Fundamentally, the loss of Mg in the calcite may reduce elasticity thereby changing the structural properties, which may affect the ability of L. glaciale to efficiently function as a habitat former in the future ocean.

Plio-Pleistocene climate sensitivity evaluated using high-resolution CO2 records.

Theory and climate modelling suggest that the sensitivity of Earth's climate to changes in radiative forcing could depend on the background climate. However, palaeoclimate data have thus far been insufficient to provide a conclusive test of this prediction. Here we present atmospheric carbon dioxide (CO2) reconstructions based on multi-site boron-isotope records from the late Pliocene epoch (3.3 to 2.3 million years ago). We find that Earth's climate sensitivity to CO2-based radiative forcing (Earth system sensitivity) was half as strong during the warm Pliocene as during the cold late Pleistocene epoch (0.8 to 0.01 million years ago). We attribute this difference to the radiative impacts of continental ice-volume changes (the ice-albedo feedback) during the late Pleistocene, because equilibrium climate sensitivity is identical for the two intervals when we account for such impacts using sea-level reconstructions. We conclude that, on a global scale, no unexpected climate feedbacks operated during the warm Pliocene, and that predictions of equilibrium climate sensitivity (excluding long-term ice-albedo feedbacks) for our Pliocene-like future (with CO2 levels up to maximum Pliocene levels of 450 parts per million) are well described by the currently accepted range of an increase of 1.5 K to 4.5 K per doubling of CO2.

A Palaeogene perspective on climate sensitivity and methane hydrate instability.

The Palaeocene-Eocene thermal maximum (PETM), a rapid global warming event and carbon-cycle perturbation of the early Palaeogene, provides a unique test of climate and carbon-cycle models as well as our understanding of sedimentary methane hydrate stability, albeit under conditions very different from the modern. The principal expression of the PETM in the geological record is a large and rapid negative excursion in the carbon isotopic composition of carbonates and organic matter from both marine and terrestrial environments. Palaeotemperature proxy data from across the PETM indicate a coincident increase in global surface temperatures of approximately 5-6 degrees C. Reliable estimates of atmospheric CO(2) changes and global warming through past transient climate events can provide an important test of the climate sensitivities reproduced by state-of-the-art atmosphere-ocean general circulation models. Here, we synthesize the available carbon-cycle model estimates of the magnitude of the carbon input to the ocean-atmosphere-biosphere system, and the consequent atmospheric pCO(2) perturbation, through the PETM. We also review the theoretical mass balance arguments and available sedimentary evidence for the role of massive methane hydrate dissociation in this event. The plausible range of carbon mass input, approximately 4000-7000 PgC, strongly suggests a major alternative source of carbon in addition to any contribution from methane hydrates. We find that the potential range of PETM atmospheric pCO(2) increase, combined with proxy estimates of the PETM temperature anomaly, does not necessarily imply climate sensitivities beyond the range of state-of-the-art climate models.

How to diagnose hypopituitarism. Learning the features of secondary hormonal deficiencies.

Hypopituitarism has many causes and various clinical presentations. Diagnosis depends on history taking, clinical suspicion, and an understanding of the hypothalamic-pituitary-target organ axes for proper interpretation of laboratory data. In the patient described in the case report, amenorrhea and inability to lactate were early clinical clues to a possible pituitary problem, but she felt otherwise fairly well over the years and did not seek evaluation. Thyroid-function tests showed normal thyrotropin measurements, but they were inappropriately low for the low T4 concentrations, indicating pituitary thyrotropin deficiency. Given the patient's obstetric history and overall clinical course, hypopituitarism resulting from postpartum pituitary necrosis was suspected. Magnetic resonance imaging of the pituitary was performed, and she was treated with glucocorticoids, T4 replacement, and estrogen-progesterone replacement. We expected her to do well. In general, the long-term outlook for patients with hypopituitarism is excellent, once the problem is diagnosed. Clinical signs and symptoms should be completely relieved by adequate hormone-replacement therapy, and with proper long-term follow-up and special attention during intercurrent illness, there should be no adverse outcomes.

Changed integrated gastrointestinal response to a mixed meal in exocrine pancreatic insufficiency.

Using a multiple-marker dilution technique to quantitate flow volumes at a jejunal sampling site 70 cm from pylorus, propulsion and absorption of a 300-ml mixed liquid test meal were compared in seven patients with exocrine pancreatic insufficiency and in ten healthy subjects. In pancreatic insufficiency, outputs of lipase and amylase were 8% of control levels. Early gastric emptying rate was similar in both groups, but emptying was completed earlier, and less gastric acid was emptied in pancreatic insufficiency. In pancreatic insufficiency, initial biliary output was larger than in controls, and transit time through the test segment was twice that of controls. During the prolonged transit time, larger amounts of glucose (but less fat) were absorbed in pancreatic insufficiency. Forty minutes after the meal, almost a third of the fatty content of the meal was propelled to lower parts of the intestine. In conclusion, pancreatic insufficiency is associated with impaired inhibitory regulation of gastric and biliary outputs after a mixed meal. The impaired digestion of nutrients in pancreatic insufficiency is partially compensated for by slowing of intestinal transit, permitting more efficient absorption. Exposure of the gut to large quantities of fat is suggested to trigger the slowing of upper intestinal transit in pancreatic insufficiency.

Apparent risk factors for chronic and acute pancreatitis in Stockholm county. Spirits but not wine and beer.

In Stockholm county, the incidences of hospitalizations for chronic pancreatitis, acute, nongallstone associated pancreatitis, and alcoholic liver disease peaked at 14.1, 40.1, and 24.3/100,000 population in 1974 for the first two conditions, and in 1979 for the last one. After the peaks, a steady decline was seen for each condition. Furthermore, the apparent national and Stockholm prevalence of chronic pancreatitis displayed a decline during 1971-1987. A concomitant decline in the Stockholm sales figures of distilled spirits from 9.2 to 5.4 1/person/yr was also observed, whereas the sales figures for wine and beer increased, leaving the overall alcohol purchase unchanged. Thus, the consumption of distilled spirits, but not that of wine and beer, appear as a risk factor for these diseases in Stockholm county.

Differing effects of ethanol on in vitro stimulated pancreatic enzyme secretion in ethanol-fed and control rats.

The single most important risk factor for chronic and acute pancreatitis is the abuse of ethanol, which, theoretically, could affect the pancreas by interacting either with some of its cell receptors or with any of its intracellular signal transduction mechanisms. Therefore, we determined in isolated pancreatic acini from 3 month ethanol-fed rats and controls the dose-response effects of secretagogues on enzyme secretion, both in the presence and absence of ethanol in the incubation medium. In ethanol-fed rats, pancreatic amylase activity was decreased by 40%, compared to controls (with identical carbohydrates intakes), whereas lipase and trypsinogen activities were unaffected. With no ethanol in the incubation medium, basal enzyme releases and enzyme dose-response curves to CCK-8, VIP, secretin, bombesin, and bethanechol were essentially unchanged in ethanol-fed rats compared to controls. In contrast, with 0.1 M ethanol present in the medium, enzyme responses to VIP, secretin, and CCK-8 were inhibited and that to CCK-8 also shifted to the right in ethanol-fed rats compared to controls. Hence, if rechallenged to ethanol, acini from ethanol-fed rats show inhibited secretions, in response to two secretagogues acting through the release of cyclic AMP, and an inhibited and right-shifted secretory response to CCK.

Does ethanol exert its effect on the canine pancreas by mediation of cholinergic nerves?

Previous studies had shown an atropine sensitive, excitatory action of i.v. ethanol on pancreatic protein secretion in alcohol fed dogs and also an increased intrapancreatic acetylcholine activity. In an attempt to clarify these observations, the dose-inhibition effect of atropine, the dose-response effect of a cholinergic agonist and the effect of vagal stimulation on pancreatic protein output in alcoholic and normal dogs was compared. The inhibitory effect of atropine and the effect of vagal stimulation were unchanged but the sensitivity to exogenous cholinergic stimulation was decreased in alcoholic dogs compared to normals. It is suggested, that the chronic repetitive ethanol exposure of acinar muscarinic receptors, desensitizes them to cholinergic stimulation but induces paradoxical sensitivity to ethanol, while the interaction of atropine is left unchanged. The increased availability of acetylcholine would only be an adaptive phenomenon to the desensitization.

Steroid profiles in urine and plasma of alcoholics during withdrawal.

Metabolic profiles of steroids in urine and plasma were analyzed in 14 male and four female alcoholics during withdrawal. The daily excretion of 30 conjugated steroids in urine and the concentration of 13 steroid sulfates in plasma were measured on days 1, 7 and 29 of the period of observation, which started on day 5-7 of abstinence. While the total excretion of cortisol metabolites was normal in most cases, the profiles of metabolites were changed in the alcoholics during the period of observation. The ratio between tetrahydrocortisol and tetrahydrocortisone exceeded the mean normal value by more than one standard deviation in 97% of the samples analyzed. The same was true of the ratio between 20-hydroxy and 20-oxosteroids in 90% of the samples. The differences between alcoholic and healthy subjects were statistically significant (p less than 0.001). The major change in plasma was a significantly increased concentration of 5-androstene-3 beta, 17 beta-diol disulfate on the first day of the study. The concentration decreased to normal values during the first month of withdrawal. The rate of excretion of this steroid in urine was increased in half of the patients and also decreased with time. The rate of excretion and the degree of fatty infiltration in liver biopsies were positively correlated. It is suggested that the ratios between cortisol metabolites in urine might be of value as biochemical markers in alcoholism, and that the absolute or relative concentrations of steroid disulfates in plasma might serve as an indicator of recent alcohol intake.

Vagal influence on exocrine pancreas of alcohol-fed and of normal dogs.

A histochemical study has indicated increased activity of acetylcholine in the pancreas of chronic alcoholic dogs, and we have recently reported decrease pancreatic responsiveness to cholinergic stimulation in such dogs. This prompted us to determine, in chronic alcoholic dogs, the net pancreatic response to stimulation mediated by cholinergic nerves. Therefore, the pancreatic response to vagal stimulation by intravenous 2-deoxy-d-glucose (2DG) infusion was examined in such dogs and in controls. After 2DG, 100 mg kg-1, significant and similar increases in protein output up to maximally 2.7 +/- 0.8 and 2.3 +/- 0.5 mg kg-1 (15 min)-1 were observed in control and alcohol-treated dogs. A significant rise in flow rate and HCO-3 output up to maximally 0.26 +/- 0.07 ml kg-1 (15 min)-1 and 43 +/- 13 mumol kg-1 (15 min)-1, respectively, occurred in the controls but was delayed in the alcoholics. The finding in alcoholic dogs of no change in protein response to 2DG is not in favour of a primary increase of vagally mediated pancreatic protein secretion. It could, however, be compatible with a primary increase in cholinergic receptor resistance due to alcohol and secondary adaptive increase in cholinergic activities, which when combined, would yield no net change of the cholinergically mediated protein response.

Cholinergic stimulation and inhibition of pancreatic secretion in alcohol-adapted dogs.

There is indirect evidence of increased release of acetylcholine in the exocrine pancreas of chronically alcoholic dogs. Our aim was to ascertain whether altered pancreatic responsiveness to cholinergic stimulation was an associated phenomenon. Pancreatic dose-response tests with graded bethanechol stimulation on constant secretion stimulation, without or with a low dose of background atropine, were performed in four chronic gastric and duodenal fistula dogs after 3 and 12 months of intragastric feeding with ethanol. The secretory protein response was dose-dependently increased by bethanechol in the control dogs but not in the test dogs, after 3 or 12 months of daily alcohol. They responded significantly only to a dose four to eight times greater than the minimum effective dose in the control dogs. Atropine depressed the entire dose-response curve of these dogs but only the response to the greatest doses in the alcohol-treated dogs. In previous experiments caerulein and/or secretin evoked increased secretory responses of bicarbonate in chronically alcoholic dogs, but this was not the case in this study with bethanechol, which did not have a stimulating effect on bicarbonate in either test or control dogs. Concomitant atropine, however, unmasked a bicarbonate-stimulating effect of bethanechol in control but not in treated dogs. It is concluded that chronic alcohol-feeding, already after 3 months, leads to a diminished pancreatic responsiveness to cholinergic stimulation and inhibition of protein output, as evidenced by at least a fourfold increase of the minimum effective dose of bethanechol and diminished inhibitory action of atropine.

Repeated I. V. injections of calcium salts give rise to increased exocrine pancreatic cell sensitivity to caerulein and urecholine in the dog.

The persisting modifications induced by repeated intravenous infusion of calcium salts were investigated in five dogs with Thomas fistulae. Five control dogs were also tested. In calcium treated dogs the pancreatic secretion stimulated by graded doses of either caerulein or urecholine showed: a) an increase in the sensitivity of acinar cells to caerulein and urecholine and potentiation by caerulein of the water and bicarbonate response to secretin, in contrast to the decreased sensitivity to secretin alone reported previously. b) an inhibition of water and bicarbonate secretion with urecholine stimulation, c) an inhibition of calcium secretion which was significant with caerulein. These findings could explain the data previously observed on basal pancreatic secretion of calcium treated dogs such as protein hypersecretion with protein precipitates and reduced bicarbonate secretion which are similar to modifications observed in chronic alcoholic dogs and men. These results have a clinical relevance to the understanding of the pathology of chronic pancreatitis.

Disappearance of an inhibitory factor of exocrine pancreas secretion in chronic alcoholic dogs.

In non-alcoholic dogs the exocrine pancreatic response to caerulein, but not to urecholine or secretin alone, was increased by atropine. This indicated a pancreatic inhibition triggered by the caerulein stimulation and blocked by atropine. The present aim was to examine whether atropine had a similar action on the caerulein-stimulated pancreatic secretion in dogs submitted to long-term alcohol feeding. Alcohol-fed dogs showed an increased volume and bicarbonate response to submaximal caerulein but a non-modified protein response as compared with the responses before alcohol adaptation. The elevated water and bicarbonate responses were not further enhanced by atropine, which, in contrast, enhanced the responses of normal dogs to such an extent as to equalize their responses with those of the treated dogs. Atropine, 5 micrograms X kg-1 X h-1, enhanced similar protein responses to submaximal caerulein more in normal than in alcohol-fed dogs, but with an eightfold higher atropine dose no enhance was produced in dogs alcohol-fed for 36 months. This dose of atropine still evoked a small and similar enhancement in the normal and 9-month-treated dogs. The enhancing action of atropine on caerulein-stimulated secretion, present in normal dogs, hence diminishes and finally disappears as a result of chronic alcohol feeding.

Early increased pancreatic secretory capacity during alcohol adaptation in the dog.

Pancreatic secretion of bicarbonate and protein in response to graded secretin administration with and without concomitant 5 micrograms . kg-1 . h-1 atropine was examined in gastric and duodenal fistula dogs after 6 and 12 months of 2 g.kg-1.day-1 ethanol intake. Maximal responses of water and bicarbonate were significantly increased after 6 months of alcohol treatment compared with untreated animals, from 12.3 to 18.1 ml/10 min for volumes and from 1.76 to 2.63 meq/10 min for bicarbonate outputs. No further increase occurred during the following 6 months. The sensitivity to secretin was not changed, and the atropine dose did not affect the responses. The protein output in the untreated dogs was constant at 12.8 mg/10 min at all secretin doses and was reduced by 50% by concomitant atropine. Long-term administration of ethanol seemed to induce a dose-related increase of the protein response to secretin, the maximal output being 30.9 mg/10 min. The infused dose of atropine shifted the dose-response relationship to the right, thus making it more evident. Six months' alcohol treatment thus increased the secretory capacity of the pancreas in response to secretin. The increased volume and bicarbonate responses are best explained by the previously described neogenesis of ducts in alcohol-fed dogs. The increased protein response is assumedly due to the here-described appearance of acinar cell responsiveness to secretin.

Response of the exocrine pancreas to graded doses of secretin in calcium-treated and normal dogs.

Persisting modifications induced by repeated intravenous calcium infusion (acute hypercalcaemia) were investigated in 6 Thomas fistula dogs: 4 controls and 4 calcium-treated dogs, two of which were studied as controls. (a) The pancreatic response to graded doses of synthetic secretin (water and bicarbonate outputs) was significantly reduced in calcium-treated dogs when compared with controls. As both the D50 for secretin-induced response increased, and the maximal secretory response decreased, if may be concluded that calcium treatment decreased the sensitivity of duct cells to secretin and reduced their secretory capacity. (b) A similar dose-response relationship was observed between secretin and pancreatic calcium outputs in controls and calcium-treated dogs. The secretin induced pancreatic calcium secretion was independent of protein secretion and latter not being modified by secretin. Thus it may be assumed that the secretory fluid calcium originated form a protein independent pool and had a dose-dependent relationship to secretin. (c) These results help to illuminate the aetiology of chronic pancreatitis induced by acute hypercalcaemia and by hyperparathyroidism.

Cholinergic secretory and inhibitory mechanisms in canine pancreatic secretion.

Dose-response relationships for pancreatic stimulants and the interactions by atropine were studied in conscious gastric and duodenal fistula dogs. Secretin, caerulein, and bethanechol, the two latter against background secretin, induced similar maximal secretions of water and bicarbonate, and maximal protein outputs with the two latter were not different. Actions of atropine differed according to type and dose of stimulant, dose of atropine, and secretory variable studied. In the dose interval of 10-40 microg x kg(-1) x h(-1), atropine suppressed the secretin-stimulated water and bicarbonate, but these or lower doses enhanced the response to submaximal caerulein. The secretion after 200 microg x kg(-1) x h(-1) or less bethanechol was unaffected by atropine, but the suppressed response to higher bethanechol doses was reversed and enhanced. These findings are compatible with the presence of one ductal secretory process sensitive to cholinergic influence in three ways: one secretory, partly atropine-sensitive, required for submaximal secretin's optimal action; one secretory, stimulated by bethanechol, and atropine-resistant; and one inhibitory, atropine-sensitive, triggered by caerulein (and high doses of bethanechol). Atropine at low doses inhibited the protein output by bethanechol but enhanced the submaximal caerulein response, which again indicates the presence of an inhibitory atropine-sensitive cholinergic principle. It is proposed that pancreatic polypeptide may be the mediator of this inhibition and that vasoactive intestinal polypeptide could be the mediator of the atropine-resistant cholinergic stimulation of water and bicarbonate secretion.