Enhanced Intestinal Absorption of Oxytocin Peptide Analogues in the Absence of Pancreatic Juice in Pigs

Purpose. The present investigation was done to study the intestinal absorption of three oxytocin peptide analogues and to elucidate the role of pancreatic juice on their absorption. Methods. In conscious chronically catheterized pigs (6–8 weeks of age) plasma concentration of the peptides, [Mpa¹, D-Tyr(Ethyl)², Thr⁴, Orn⁸]-oxytocin (F314), [Mpa¹, D-Tyr(Ethyl)², Val⁴, D-Arg⁸]-oxytocin (CAT), and [Mpa¹, D-Tyr(Ethyl)², Thr⁴, Orn⁸, desGly⁹, carba⁶]-oxytocin (F327) after intraduodenal administration, during presence or diversion of the pancreatic juice via a pancreatic duct catheter, were determined by radioimmunoassay. The stability of the peptides to degradation was determined in vitro by incubation with activated pancreatic juice, chymotrypsin or trypsin, followed by reversed phase HPLC analyses. Results. All peptides were absorbed with a bioavailability of about 0.5% in the presence of pancreatic juice, but increased to 1.0%, 2.1%, and 13.5% for F314, CAT, and F327, respectively, when the pancreatic juice was diverted from the intestine. After incubation with pancreatic juice 95% of F314, 98% of F327, and 100% of CAT was found intact. When incubated with trypsin CAT remained intact while F314 and F327 were degraded by 54% and 46%, respectively. Incubation with purified chymotrypsin did not degrade the test peptides. Conclusions. The results indicate that the increased absorption of peptides observed under conditions of diverted pancreatic juice cannot only be explained by the absence of pancreatic enzymes, but also by changed absorptive properties in the gastrointestinal tract.     

Corneal D.C. recordings of slow ocular potential changes such as the ERG c-wave and the light peak in clinical work

A set-up for D.C. recordings of slow ocular potentials such as the c-wave of the electroretinogram (ERG) as well as the fast oscillation (FO), the light peak (LP) and the dark trough (DT) in both clinical and experimental work is described. It includes matched calomel half-cells connected by saline-agar bridges to a corneal contact lens on the eye and a reference chamber on the forehead, a low-drift differential-input D.C. amplifier, an A/D converter, a computer, a thermoprinter, a flexible disc memory, a plotter, and a device for light stimulation controlled by the computer.Examples of the usefulness of the set-up in clinical work are shown in the form of D.C. c-wave ERGs of normal subjects as well as of patients with vitelliform macular degeneration, choriocapillaris atrophy, and retinitis pigmentosa. The direct corneal recording of the FO and LP is demonstrated as well. The different origins of the standing potential (SP) of the eye, the ERG c-wave, the FO and the LP are reviewed briefly.     

Intravenous Immunoglobulin Treatment of Recurrent Miscarriage： an Update of Placebo-controlled Trials

Recurrentmiscarriage (RM) isdefined as three ormoreconsecutivemiscarriagesand affects 0 .5～ 1 .0 % of all women.In less than 1 0 % of the couples a parentalchromosome abnormality ora significantuterine abnormality can be demonstrated ascauses.Some cases …     

Blue Hue in the Dermoscopy Setting: Homogeneous Blue Pigmentation, Gray-Blue Area, and/or Whitish Blue Veil?

In dermoscopy, the correct recognition of the single parameters is fundamental to achieve great diagnostic accuracy, but the scarce morphologic expression of a parameter may lead to diagnostic errors. We report the case of a 27-year-old white man presenting a pigmented lesion of the back, which was present since puberty. Clinical examination revealed on the back the presence of a flat, gray-blue lesion and at the periphery a small dark-brown papule. An assessment of the lesion by means of dermoscopy was performed. The purpose of this report was to analyze the Blue Hue in dermoscopy with its histopathologic correlates, starting with the discussion of a clinical case.     

Potential impact on tumor control and organ preservation with cisplatin and 5-fluorouracil for patients with advanced tumors of the paranasal sinuses and nasal fossa. A prospective pilot study.

METHODS. Twelve patients with advanced epithelial nonadenocarcinoma of the paranasal sinuses and nasal fossa were treated with three cycles of cisplatin (100 mg/m2, day 1) and 5-fluorouracil (1000 mg/m2/24 hours on days 1-5 by continuous infusion), followed by preoperative external radiation therapy of 48 Gy and limited surgery, clearing the paranasal sinuses and nasal fossa. RESULTS. After chemotherapy, 11 of 12 patients were free of the previous symptoms of disease. Clinical response rates were different, however, with an overall response rate of approximately 70% with no complete responses. Histopathologic analysis of resected specimens showed no vital tumor in eight patients, minimal microscopic disease in three patients, and infiltrating tumor in one patient. Local control was achieved in 11 of 12 patients. Ten patients are alive with no evidence of disease (mean follow-up, 27 months). Surgical mutilation was avoided, with no functional or cosmetic loss. CONCLUSIONS. The results of this small pilot study seem to indicate a high chemosensitivity of carcinomas of the paranasal sinuses and nasal fossa, which, in this study, has meant significant relief of symptoms and an unusually high rate of local control (90%) without mutilation.     

Early neuromuscular customized training after surgery for lumbar disc herniation: a prospective controlled study

A prospective and controlled study of training after surgery for lumbar disc herniation (LDH). The objective was to determine the effect of early neuromuscular customized training after LDH surgery. No consensus exists on the type and timing of physical rehabilitation after LDH surgery. Patients aged 15–50 years, disc prolapse at L4–L5 or L5–S1. Before surgery, at 6 weeks, 4, and 12 months postoperatively, the following evaluations were performed: low back pain and leg pain estimated on a visual analog scale, disability according to the Roland–Morris questionnaire (RMQ) and disability rating index (DRI). Clinical examination, including the SLR test, was performed using a single blind method. Consumption of analgesics was registered. Twenty-five patients started neuromuscular customized training 2 weeks after surgery (early training group=ETG). Thirty-one patients formed a control group (CG) and started traditional training after 6 weeks. There was no significant difference in pain and disability between the two training groups before surgery. Median preoperative leg pain was 63 mm in ETG and 70 mm in the CG. Preoperative median disability according to RMQ was 14 in the ETG and 14.5 in the CG. Disability according to DRI (33/56 patients) was 5.3 in the ETG vs. 4.6 in the CG. At 6 weeks, 4 months, and 12 months, pain was significantly reduced in both groups, to the same extent. Disability scores were lower in the ETG at all follow-ups, and after 12 months, the difference was significant (RMQ P=.034, DRI P=.015). The results of the present study show early neuromuscular customized training to have a superior effect on disability, with a significant difference compared to traditional training at a follow-up 12 months after surgery. No adverse effects of the early training were seen. A prospective, randomized study with a larger patient sample is warranted to ultimately demonstrate that early training as described is beneficial for patients undergoing LDH surgery.     

Medical abortion in the first trimester: the use of serum hCG and endometrial thickness as markers of completeness.

OBJECTIVE: The combination of mifepristone and misoprostol is an established method for induction of early first trimester abortion, but there is no consensus about the best evaluation of treatment outcome. We assessed endometrial thickness, determined by ultrasound and serum-human chorionic gonadotropin (s-hCG) as markers of successful management. METHODS: Prospective trial involving 255 women, with a gestation of 62 days or less, who were to undergo medical abortion. In addition to our established routines of performing clinical and ultrasound examinations, we also determined the s-hCG level prior to treatment and at follow-up. RESULTS: Of the 255 subjects treated during the study, 20 (7.8%) were lost to follow-up. The overall complete abortion rate was 94.0%. Fourteen subjects required vacuum aspiration, nine of them prior to the scheduled follow-up and five thereafter. None of the pregnancies were ongoing. A decrease of 99% in s-hCG levels was noted in 99% of the women, when levels determined prior to mifepristone intake and those measured 15-71 days post-abortion were compared. CONCLUSION: This study confirms that s-hCG levels drop sharply after medical abortion. To assess the completeness of medical abortion, we recommend that clinical examination to be combined with determination of s-hCG. Ultrasonography should be carried out only when indicated.     

Attempts to define the minimal serum level of vitamin A required for normal visual function in a patient with severe fat malabsorption

A case with severe malabsorption of fat soluble vitamins is described. The malabsorption developed after an intestinal bypass operation due to morbid obesity. Night blindness occurred as the first symptom of vitamin A deficiency. The cone visual sensory threshold was elevated about one log unit and the rod threshold abot two and a half log units. No changes of the a- and b-waves of the electroretinogram (ERG) was observed. However, during the initial phase of very low serum reninol level (0.21 mumol/l) the summed amplitudes of the oscillatory potentials (OPs) were lower. After parenteral therapy with vitamin A the night blindness disappeared and the dark-adapted rod and cone threshold sensitivity recovered to normal. However, the time-course of rod adaptation first reached normal levels after 5 months. The amplitudes of the OPs of the ERG response returned to normal when the serum retinol level had increased close to normal. Serum retinol levels of 0.7 mumol/l or higher were always associated with normal or close to normal dark-adapted rod sensitivity. However, a normal serum retinol level (> 0.95 mumol/l) and a normal dark-adapted rod threshold sensitivity were not always associated with a normal time-course of the rod adaptation. It is concluded, that the maintenance dosage of vitamin A must be individualized and that patients who have undergone jejuno-ilea bypass surgery must be carefully monitored for vitamin A deficiency by both serum levels and dark adaptation measurements.     

Hippocampal Noradrenaline and Serotonin Release over 24 Hours as Measured by the Dialysis Technique in Freely Moving Rats: Correlation to Behavioural Activity State,Effect of Handling and Tail-Pinch

Hippocampal extracellular levels of noradrenaline (NA), 5-hydroxytryptamine (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) were monitored with the microdialysis technique in freely moving rats. In one experiment 30 min samples were collected during 24 h of continuous perfusion, and the monoamine output was compared to the behavioural activity state, as arbitrarily classified in three categories: sleep/rest, drowsiness and full alertness associated with complex behaviours. In the individual animal the hippocampal NA and 5-HT output showed pronounced fluctuations during the 24 h period, but the 30 min sampling times did not allow for a clear-cut correlation to behavioural activity state. However, the mean NA and 5-HT output for all animals during the dark period of the day was 43 and 38% higher, respectively, than during the light period, and the average NA and 5-HT levels in samples collected during periods of high behavioural activity was 34 and 45% higher, respectively, than during periods of rest or sleep. In contrast, there were no detectable changes in extracellular 5-HIAA. The selective serotonin uptake blocker indalpine, added to the perfusion fluid at 1 microM, increased the extracellular 5-HT levels 6-fold, with a similar correlation to behavioural activity state as without indalpine. In a second experiment the effect of handling and tail-pinch was studied in 15 min sample fractions. Gentle handling of the animals during the sampling period increased the hippocampal NA and 5-HT output by 32 and 72%, respectively, and a similar increase (63 and 48%) was obtained by application of tail-pinch. Maximum NA output was reached during the handling or tail-pinch period, whereas maximal 5-HT levels were detected in the subsequent 15 min sample fraction. No changes in extracellular 5-HIAA was observed. It is concluded (1) that intracerebral microdialysis provides a useful method for the study of extracellular NA and 5-HT in the hippocampal formation of conscious rats during active behaviour; (2) that there are substantial fluctuations in hippocampal NA and 5-HT output in freely moving rats which correlate with the light - dark cycle as well as with the activity state of the animals; (3) that the spontaneous variations in 5-HT output are maintained during reuptake blockade; and (4) that behavioural activation through gentle handling or tail-pinch elicits NA and 5-HT release. The present data support a role of the forebrain NA and 5-HT systems in behavioural state control and highlights the necessity of experimental designs in which the spontaneous fluctuations in transmitter release are controlled for in studies of, for example, drug effects on NA and 5-HT release in conscious animals.     

Intrinsic Organization and Connectivity of Intrastriatal Striatal Transplants in Rats as Revealed by DARPP-32 Immunohistochemistry: Specificity of Connections with the Lesioned Host Brain

Intrastriatal grafts of tissue obtained from the striatal or neocortical primordia of rat fetuses have been studied with respect to their intrinsic organization and connectivity using antibodies to DARPP-32 in combination with acetylcholinesterase (AChE) histochemistry, tyrosine hydroxylase (TH) immunocytochemistry, and anterograde and retrograde axonal tracing techniques. The striatal grafts were characterized by distinct patches of DARPP-32-immunoreactive neurons, which were identical to the densely AChE-positive patches stained in adjacent sections from the same specimens. The non-patch areas possessed only few DARPP-32-positive neurons and contained only sparse AChE-positive fibres. The cortical grafts, by contrast, contained no neurons with clear-cut DARPP-32-positivity and they exhibited a sparse, evenly distributed AChE fibre network, similar to that seen in the non-patch areas of the striatal grafts. The host dopaminergic afferents, as revealed by TH immunostaining, had grown selectively into the DARPP-32-positive patches in the striatal grafts, where they formed a dense terminal network around the DARPP-32-positive cell bodies. The non-patch areas, as well as the cortical grafts, received only sparse TH innervation. By contrast, the host cortical afferents, labelled by Phaseolus vulgaris leucoagglutinin from the host frontal cortex, were seen to extend into both the patch and non-patch areas of the striatal grafts. Transplant neurons projecting into the host brain were labelled by Fluoro-Gold injections into the ipsilateral host globus pallidus. These injections labelled large numbers of medium-sized neurons within the striatal grafts and the vast majority of them (over 85%) were confined to the DARPP-32-positive patches. Similar Fluoro-Gold injections labelled only few graft neurons in the cortical grafts. The results indicate that the striatal grafts are composed of a mixture of striatal and non-striatal tissue, and that the striatal graft compartment selectively establishes afferent and efferent connections with the host nigro-pallidal system. These graft connections demonstrate a remarkable specificity in the formation of graft - host connectivity. The results, moreover, suggest that developmental properties of the grafted striatal primordium are retained and expressed in the implanted cell suspension, and that the neuronal systems of the lesioned adult host brain, at least to some extent, remain responsive to growth regulating mechanisms normally operating during ontogenetic development.