Insulin receptor activation in the nucleus accumbens reflects nutritive value of a recently ingested meal.

With respect to feeding, insulin is typically thought of as a satiety hormone, acting in the hypothalamus to limit ingestive behavior. However, accumulating evidence suggests that insulin also has the ability to alter dopamine release in the striatum and influence food preferences. With increased access to high calorie foods, Western societies have a high prevalence of obesity, accompanied by insulin insensitivity. Little is known about how insulin is trafficked into the brain following food consumption and whether insulin insensitivity in the periphery is mirrored in the central nervous system. We investigated insulin receptor activation in the ventral striatum of rats receiving water or 16% glucose either orally or intragastrically. We also investigated whether glucose-induced insulin receptor activation was altered in food-restricted (FR) or diet-induced obesity (OB) rat models. Lastly, we examined whether insulin plays a significant role in flavor-nutrient preference learning. Glucose intake stimulated a rapid increase in insulin receptor activity in the ventral striatum of FR and ad libitum (AL) fed rats, but not OB rats. Similarly, both AL and FR, but not OB rats demonstrated significant flavor-nutrient preferences. However AL rats receiving brief inhibition of insulin activity during conditioning failed to acquire a significant flavor-nutrient preference. These findings suggest that impaired insulin receptor activation in the ventral striatum may result in inaccurate valuation of nutritive foods, which could lead to overconsumption of food or the selection of foods that don't accurately meet the body's current physiological needs.

Unilateral inactivation of the basolateral amygdala attenuates context-induced renewal of Pavlovian-conditioned alcohol-seeking.

Environmental contexts associated with drug use promote craving in humans and drug-seeking in animals. We hypothesized that the basolateral amygdala (BLA) itself as well as serial connectivity between the BLA and nucleus accumbens core (NAC core) were required for context-induced renewal of Pavlovian-conditioned alcohol-seeking. Male Long-Evans rats were trained to discriminate between two conditioned stimuli (CS): a CS+ that was paired with ethanol (EtOH, 20%, v/v) delivery into a fluid port (0.2 mL/CS+, 3.2 mL per session) and a CS- that was not. Entries into the port during each CS were measured. Next, rats received extinction in a different context where both cues were presented without EtOH. At test, responding to the CS+ and CS- without EtOH was evaluated in the prior training context. Control subjects showed a selective increase in CS+ responding relative to extinction, indicative of renewal. This effect was blocked by pre-test, bilateral inactivation of the BLA using a solution of GABA receptor agonists (0.1 mm muscimol and 1.0 mm baclofen; M/B; 0.3 µL per side). Renewal was also attenuated following unilateral injections of M/B into the BLA, combined with either M/B, the dopamine D1 receptor antagonist SCH 23390 (0.6 µg per side) or saline infusion in the contralateral NAC core. Hence, unilateral BLA inactivation was sufficient to disrupt renewal, highlighting a critical role for functional activity in the BLA in enabling the reinstatement of alcohol-seeking driven by an alcohol context.

Influence of substrate and/or neurohormonal mimic on in vitro pancreatic enzyme release from calves postruminally infused with partially hydrolyzed starch and/or casein.

Our objectives were to determine the effects of neuroendocrine challenge and substrates on in vitro alpha-amylase and trypsin release in pancreatic tissue collected from Holstein calves (n = 24; 88 +/- 3 kg) abomasally infused for 10 d with tap water (control), partially hydrolyzed starch (SH; 4 g/[kg of BW x d]) and/ or casein (0.6 g/[kg of BW x d]). The caudal portion of the pancreas was removed, rinsed with ice-cold saline, cut into approximately 2 x 2-mm segments, and incubated in oxygenated Krebs Ringer bicarbonate buffer containing no substrate (control), glucose, amino acids, or VFA at 39 degrees C. After 60 min of incubation, neurohormonal mimics (none; control), carbachol (acetylcholine analog; 10 microM final), or caerulein (cholecystokinin mimic; 100 nM final) were added to the flasks and tissue was incubated for 60 min. Pancreatic tissue concentrations and in vitro release of alpha-amylase and trypsin decreased (P < 0.001) in calves abomasally infused with SH. Carbachol increased (P < 0.10) alpha-amylase and trypsin release in tissue collected from all calves. An effect of caerulein to increase alpha-amylase release (P < 0.10) was only observed with prior exposure to abomasal casein infusion in vivo or with simultaneous incubation with amino acids in vitro. Caerulein increased (P < 0.10) trypsin release in tissue collected from all calves except for those receiving SH + casein. Glucose decreased (P < 0.10) alpha-amylase release from pancreatic tissue collected from calves receiving abomasal control and casein treatments. Amino acids decreased (P < 0.10) alpha-amylase and trypsin release from pancreatic tissue collected from calves receiving the abomasal control treatment. Glucose, amino acids, and VFA decreased (P < 0.10) trypsin release from tissue collected from calves receiving abomasal SH. These data indicate that carbachol can stimulate pancreatic enzyme release in vitro. Caerulein, however, is only effective in stimulating in vitro pancreatic enzyme release in tissue from calves with an increased postruminal protein supply or in tissue incubated with amino acids. The results indicate that postruminal and local nutrients might be important in altering the responsiveness to a neuroendocrine challenge and could be an important regulatory event involved with dietary adaptation in ruminants.

Postruminal administration of partially hydrolyzed starch and casein influences pancreatic alpha-amylase expression in calves.

The objective was to examine the effects of postruminal partially hydrolyzed starch (SH) and/or casein on the expression of pancreatic alpha-amylase mRNA, protein and activity in calves. Holstein calves [(n = 24) 88 plus minus 3 kg body weight (BW)], fitted with abomasal infusion cannulas, were randomly assigned within block (week of infusion) to one of four abomasal infusion treatments. Calves were fed an alfalfa-based diet, and SH [4 g/(kg BW.d)] and/or casein [0.6 g/(kg BW.d)] was infused abomasally for 10 d before tissue collection. There was a SH x casein interaction (P < 0.10) for pancreatic weight (g and g/kg BW) because casein increased pancreatic weight in the absence of SH but did not influence pancreatic weight in the presence of SH. Pancreatic alpha-amylase mRNA tended to be lower (P = 0.06) and protein and activity (U/g pancreas and U/g protein) were lower (P = 0.02) in calves receiving abomasal SH. The concentration of pancreatic trypsin activity (U/g pancreas and U/g protein) was lower (P < 0.03) in calves receiving abomasal SH. There was a SH x casein interaction for total alpha-amylase and trypsin activity [U/pancreas and U/(pancreas.kg BW)] because casein increased total activity in the absence of SH but not in the presence of SH. These data suggest that increases in small intestinal protein flow enhance pancreatic weight and thus total pancreatic alpha-amylase and trypsin activity, yet small intestinal SH inhibits the increase in pancreatic weight resulting from increased small intestinal protein flow. Additionally, postruminal SH decreases alpha-amylase expression largely by translational events.

Measuring non-spherical optical surfaces.

INTRODUCTION: More lens designs for the presbyopic market are emerging and the use of novel constructions to generate varifocal optics in contact lenses is increasing. A number of designs incorporate aspheric shapes, of known p-values on the front and back surface of contact lenses. Frequently, the back optic zone radius quoted by the manufacturer is a nominal reference making verification of these lenses difficult. The purpose of this study was to determine whether a videokeratoscope or an optical microspherometer could verify these complex surfaces. METHODS: Fifty-four concave test surfaces of known vertex curvatures (7.30 to 8.10 mm, in 0.1 mm steps) and known p-values (1.0 to 0.0, in 0.1 steps) were produced and measured with two different systems. RESULTS: The optical microspherometer was able to verify the vertex radius to a high degree of accuracy (+/- 0.072[2SD]) without bias (mean difference = 0.008 +/- 0.01(2SE]). However, verification of the p-value by utilising Baker's equation demonstrated a poor degree of accuracy (+/-0.574) and bias (mean difference=0.134, +/-0.078). The degree of accuracy for the measurement of the vertex radius of the concave surface, when using the videokeratoscope, was also very high (+/-0.09) but with a demonstration of bias (mean difference=-0.017, +/-0.012). The videokeratoscope was able to describe the p-value for the surface to a high degree of accuracy (+/-0.136) but did demonstrate bias (-0.052, +/-0.018). These results for the measurement of the p-value for the optical microspherometry were statistically significantly different from that of the control measurement (p = 0.0379) and that for the videokeratoscope (p = 0.0042). CONCLUSION: To determine the degree of asphericity of a concave optical surface to an acceptable degree of accuracy a videokeratoscope can be used in preference to an optical microspherometer. Both instruments demonstrated a high degree of accuracy when measuring the vertex radius.

Life expectancy of rigid gas permeable and high water content contact lenses.

PURPOSE: The purpose of this study was to evaluate the life expectancy of various rigid gas permeable (RGP) lens materials used on a daily wear basis and to compare these results with the life expectancy of a matched group of soft lens wearers. METHODS: We retrospectively analyzed the records of 600 contact lens wearing patients (300 soft contact lens users and 300 RGP lens users fit between September 1987 and September 1994. None of the subjects wore lenses on a planned replacement system. For the purpose of the study, RGP lenses were divided into three groups: < or = 40 Dk were considered low-Dk; 41-89 Dk were considered mid-Dk; and > or = 90 Dk were considered high-Dk. All soft lenses were high water content lenses (> or = 60% water content). Lenses were included if they were replaced due to loss, breakage, deposition, or poor wettability but not if replaced because of changes in fit or prescription. RESULTS: The mean (+/- SD) life-spans of each lens type in months were 19.9 +/- 17 for low-Dk RGP lenses, 15.9 +/- 13.3 for mid-Dk RGP lenses, 9.0 +/- 8.2 for high-Dk RGP lenses, and 6.4 +/- 5.2 for high water content soft lenses. Statistical analysis using a one-way ANOVA on ranks indicated that these results were statistically significant (P < 0.0001). CONCLUSIONS: Patients should be informed that high-Dk lenses (RGP and soft) provide substantial clinical benefits and that they should except to replace high-Dk RGP lenses after approximately 6 months. This lends further credence to the use of high-Dk lenses on a planned replacement basis.

Regular replacement of extended wear rigid gas permeable contact lenses.

PURPOSE: While the benefits of planned replacement of soft contact lenses have been investigated, the question of whether there are any clinical benefits to planned replacement of rigid gas permeable (RGP) lenses does not appear to have been addressed experimentally. We aimed to determine the benefits of regular replacement of extended wear RGP contact lenses. METHODS: We conducted a prospective, single-center, controlled, double-masked study of 39 RGP lens wearers. The subjects were divided into two groups and wore extended wear Quantum 2 lenses (Dk = 120) for 12 months. Subjects in Group I replaced lenses every 3 months, whereas those in Group II were not scheduled to replace their lenses. The integrity of the lenses and the ocular responses to lens wear were monitored in both groups every three months. RESULTS: Compared to lenses worn by subjects in Group I, lenses worn by Group II subjects showed significantly more mucous coating, lens binding, and corneal staining over time (P < 0.05; ANCOVA). There was no difference in microcystic or tarsal conjunctiva response, lens comfort, refractive change, or visual acuity between the two groups. CONCLUSIONS: We advocate that to maintain optimal lens integrity and ocular health, RGP lenses used for extended wear should be replaced every 3 to 6 months.

A randomized comparison of multipolar electrocoagulation and injection sclerosis for the treatment of bleeding peptic ulcer.

Several options are available to the gastroenterologist for the endoscopic control of peptic ulcer hemorrhage. Sixty men (mean age, 62 years) were stratified into those with actively bleeding ulcers or ulcers with stigmata of recent hemorrhage, and then randomized to treatment with injection sclerosis or the multipolar probe until bleeding ceased. There were no significant differences between the randomized groups in terms of age, ulcer size, or transfusion requirements. We achieved hemostasis in 95% of all patients. Re-bleeding rates were 25% and 23% in patients treated with the multipolar probe and injection sclerosis, respectively. There was no significant difference in mortality (14% multipolar probe, 7% injection sclerosis). Patients over the age of 70, those whose onset of bleeding was while an inpatient, and those with an ulcer larger than 2 cm were more likely to have a poor outcome, regardless of the type of endoscopic therapy. Injection sclerosis and multipolar electrocoagulation are equally effective in controlling bleeding from peptic ulcer.

Pancreatic pseudocyst as a cause for secondary achalasia.

Secondary achalasia is commonly due to cancer. Benign causes are rare and an association with pancreatitis has never been made. Our patient presented with clinical, manometric, endoscopic, and radiographic features of achalasia that occurred in conjunction with a pancreatic pseudocyst extending into the mediastinum. Documentation of this unique relationship was made on two occasions after episodes of complicated pancreatitis and was confirmed by restoration of normal esophageal function after drainage of the pseudocyst. Onset of dysphagia occurring in association with pancreatitis suggests the presence of a pseudocyst and secondary achalasia.

The role of a highly sensitive amplified enzyme immunoassay for thyrotrophin in the evaluation of thyrotroph function in hypopituitary patients.

Using a highly sensitive amplified enzyme-linked immunoassay (AEIA) for thyrotrophin (TSH), we have assessed the ability of a single basal measurement of TSH to predict the subsequent response of TSH to TRH in a group of 11 patients with known pituitary pathology and some evidence of hypopituitarism. All patients were clinically euthyroid. Basal levels of AEIA-TSH ranged from less than 0.2 mU/l ('undetectable') to 0.9 mU/l; within this range there was no correlation with the subsequent TSH levels at 30 min in the TRH test. The TSH response in the TRH test did not correlate with the direct measurements of prevailing thyroid hormone levels (Total T4 or Free T4). We suggest that in patients with pituitary disease, the formal TRH test yields additional information regarding residual thyrotroph function that cannot reliably be predicted by a single basal TSH value, even when measured by a sensitive method. The current and potential thyroid status in patients with hypopituitarism must continue to rest on the overall picture provided by clinical assessment, direct measurement of thyroid hormones and the TRH test response. A basal TSH alone gives little useful information regarding thyroid status in such patients.

A critical analysis of the Sacks-Vine gastrostomy tube: a review of 120 consecutive procedures.

Results from 120 patients managed with a Sacks-Vine gastrostomy tube were analyzed. In our experience, this device can be successfully placed in almost all cases (96%), and has a low rate for procedure-related mortality (0.8%) and major (4.4%) and minor (12.4%) complications. Advantages and problems associated with this feeding catheter are discussed. The Sacks-Vine gastrostomy tube is a reasonable alternative to other catheters placed by different methods.

Effects of two novel dopaminergic drugs, CV 205-502 and CQP 201-403, on prolactin and growth hormone secretion by human pituitary tumours in vitro.

Two novel dopaminergic drugs, designated CV 205-502 and CQP 201-403 have recently been developed by Sandoz Pharmaceuticals Ltd (Basle, Switzerland). The effects of these drugs on PRL and GH secretion by normal rat and tumorous human pituitary cells in vitro have been investigated. Low doses of both CV 205-502 and CQP 201-403 immediately and profoundly suppressed PRL secretion, which failed to recover up to 7 h after removal of the drugs. Similarly, CQP 201-403 significantly suppressed basal GH secretion by human pituitary somatotropic tumours in culture, and both drugs significantly reduced the stimulatory effect of GHRH. These effects are more potent and longer acting than the previously described in vitro effects of bromocriptine. It is concluded that CV 205-502 and CQP 201-403 hold potential for the treatment of patients with hyperprolactinaemia and, possibly, also in patients with acromegaly.

Neuropeptide Y directly inhibits growth hormone secretion by human pituitary somatotropic tumours.

Neuropeptide Y (NPY) is a 36 amino acid peptide, widely distributed throughout the brain and is found in hypothalamic neurones. This latter finding suggests that NPY may possess a hypophysiotropic function. A number of studies have demonstrated effects of NPY on LH and GH secretion by rat pituitary cells. We report here the results of experiments investigating the effects of NPY on GH secretion by tumorous human somatotropic pituitary cells in culture. NPY (0.25-25 nmol/l) inhibited GH secretion by 20-53%, the maximal effect depending upon the tumour studied. The potency of NPY was less than that of somatostatin (SRIH). The stimulatory effects of growth hormone releasing factor (GHRH) and theophylline were reduced by NPY, but NPY did not modify the inhibitory effect of SRIH on GH secretion. It is concluded that NPY may be involved in the control of GH secretion, at least by tumorous human pituitary somatotropes.

A new fossil cebine from Hispaniola.

An incomplete mandibular fragment of a cebine monkey from an early Holocene Haitian cave deposit adds to the small but growing list of fossil Antillean primates. The jaw is of the correct size to belong to the same taxon as the partial maxilla of "Saimiri" bernensis from the Dominican Republic. Both finds probably represent a single species whose proximate ancestry lay closer to Cebus than to Saimiri, although more evidence will be required to substantiate this. No close relationship of the Hispaniolan fossils to the Jamaican platyrrhine Xenothrix is indicated. How monkeys managed to penetrate the West Indies is a biogeographical puzzle of the first order. Geographical vicariance events, island-hopping, and purposeful or inadvertent introduction by humans seem rather implausible devices. On the whole, long-distance, over-water rafting from the Americas remains the most likely mechanism for past land vertebrate immigration into the Caribbean.