Non-opiate effects of neuropeptides derived from beta-endorphin

Brain enzymes convert the opioid peptide beta-endorphin (beta E-(1-31)) to alpha- and gamma-endorphin and to several non-opioid fragments by further cleavage of the tyrosine residue or acetylation. Several of these peptides selectively affect brain functions. alpha-Endorphin (beta E-(1-16)) and relate non-opioid fragments (beta E-(2-16), beta E-(2-9) a.o.) like amphetamine, delay extinction of pole-jumping avoidance behavior and facilitate passive avoidance behavior. In addition these peptides enhance the stereotyped sniffing response induced by the injection of apomorphine into the nucleus caudatus. The fragment beta E-(10-16) inhibits, like serotonin and antidepressants, the behavioral effects of melatonin injected into the nucleus accumbens. gamma-Endorphin (beta E-(1-17)) has inherent opioid and neuroleptic-like properties, e.g. demonstrated by a naloxone reversible inhibition of hypermotility induced by apomorphine following injection into the nucleus accumbens. Also the non-opioid gamma-type endorphins (e.g. DT gamma E (beta E-(2-17) and DE gamma E (beta E-(6-17)) mimic certain effects of neuroleptics. These peptides facilitate extinction of pole-jumping avoidance behavior, attenuate passive avoidance behavior and antagonize the hypomotility and stereotyped sniffing induced by apomorphine injected into the nucleus accumbens and pyriform cortex respectively. These and other behavioral studies, including grasping responses, brain stimulation reward, food and other positively rewarded behavior, indicate that the action of alpha-type endorphins is in some aspects comparable to that of psychostimulants, while the effects of gamma-type endorphins are comparable to those of classical as well as atypical neuroleptics. Indeed, gamma-type endorphins have antipsychotic effects in a category of schizophrenic patients.     

Inhibition of lymphoma invasion and liver metastasis formation by pertussis toxin

We have examined whether pertussis toxin, an agent known to inhibit entry of normal lymphocytes into tissues, affects invasion and metastasis formation by malignant lymphoma and T-cell hybridoma cells. The toxin reduced invasion in vitro in hepatocyte cultures to 20% of control values. Inhibition was maximal after pretreatment for 2 h with approximately 100 ng/ml. The effect of pretreatment with 1 to 5 micrograms toxin/ml for 4 h persisted for at least 5 days, despite a more than 100-fold increase in cell number. The proliferation rate was not affected. Liver metastasis formation after tail vein injection of TAM2D2 T-cell hybridoma cells in syngeneic AKR mice, measured as liver weight, was reduced to 10 to 25% of controls after pretreatment of the cells for 4 h with 1 microgram pertussis toxin/ml. Metastasis to kidneys, ovaries, and lymph nodes was not, or less evidently, affected. With MB6A lymphosarcoma cells no effect was seen after treatment with 1 microgram/ml, but a significant reduction of the liver tumor burden to approximately 50% of controls was achieved by treatment with at least 5 micrograms toxin/ml. Spleen metastasis by MB6A cells was not affected. These results provide evidence for a similarity in invasion mechanisms of normal and malignant lymphoid cells, and they suggest that invasiveness is an important factor in the formation of lymphoma metastases, particularly in the liver.     

Cyanosis and cardiovascular depression in a neonate: complications of halothane anesthesia or phenylephrine eyedrops?

A 3-week-old patient underwent cataract extraction under halothane anesthesia. After induction of anesthesia and instillation of phenylephrine hydrochloride eyedrops, the patient experienced cyanosis and cardiovascular depression. Her condition improved over the next 10 minutes. The possible contributions of halothane and phenylephrine to this response are discussed.     

Gastroduodenal mucosal hemodynamics by endoscopic reflectance spectrophotometry

The reflectance spectrophotometric technique measures an index of mucosal hemoglobin concentration and an index of oxygen saturation by spectral analysis of light reflected from the mucosal surface. Using a commercially available unit, a technique for obtaining reproducible endoscopic measurements with acceptable intraobserver and interobserver variability was developed in the anesthetized dogs. The reflectance spectrophotometric finding that experimentally induced prehepatic portal hypertension did not affect gastric mucosal blood flow was confirmed by hydrogen gas clearance measurements. Endoscopic studies in patients with active duodenal ulcer disease revealed a higher index of mucosal hemoglobin concentration and a normal index of oxygen saturation (i.e., an increase in blood flow) at the margin of the ulcer compared with the adjacent normal appearing mucosa.     

Phase mapping from left ventricular radionuclide ventriculograms: interobserver reliability and accuracy of the programme

Phase analysis of data from radionuclide ventriculograms is known to provide space-time information on the mechanical emptying of pixels located in the ventricular regions. It could therefore perhaps be useful for detecting abnormal sequences of contraction of the ventricles as well as to localize sites of premature electromechanical action. The phase programme used in this investigation is designed to trace the electromechanical action of the ventricles from colour-coded phase images (first harmonic Fourier transform), not only visually from a cinematic representation, but particularly from a data output of x, y coordinates and phase angles of sites chosen as they empty in the ventricular regions. Six healthy baboons were subjected to conventional radionuclide ventriculography, performed hourly for the duration of 11 h under anaesthesia. The programme was used by two independent observers to map the progression of emptying for each of the thus acquired 66 left ventricular phase images. The interobserver reliability and the accuracy achieved in mapping normal contraction patterns was found to be good. Abnormalities which appeared during the prolonged anaesthesia and which were confirmed with 12 lead electrocardiography were likewise detected consistently.     

Glycolytic enzymes in breast cancer, benign breast disease and normal breast tissue

The activities of hexokinase, phosphofructokinase, aldolase, enolase and pyruvate kinase were studied in breast cancer tissues, in comparison to benign breast disease and normal breast tissues. The enzyme activities in breast cancer were significantly increased compared to normal and benign breast tissues (p less than 0.001). Also the increase in activity in benign disease compared to normal was statistically significant (p less than 0.001). Within the group of benign diseases, fibroadenomas could be distinguished from fibrocystic disease, the former generally showing higher activities compared to the latter (p less than or equal to 0.05). Carcinoma subgroups, classified according to their histology, could not be recognized enzymologically. In addition, isozyme composition of pyruvate kinase and enolase was studied. We did not find a significant shift towards K type pyruvate kinase expression in benign disease compared to normal breast tissues. Also fibroadenomas did not differ from fibrocystic disease. However, the amount of K type pyruvate kinase in carcinomas proved to be significantly higher in comparison to benign disease and normal breast tissues (p less than 0.001). Expression of alpha gamma-enolase in normal breast tissue was virtually absent. In benign disease only a minority of specimens did show the hybrid alpha gamma-enolase. Nearly all carcinomas had alpha gamma-enolase expression and in 20% of the carcinomas gamma gamma-enolase could be detected (so-called neuron-specific enolase). By discriminant analysis, the function giving the best discrimination compared to the histological data was based on natural logarithm aldolase and the total of gamma-enolase subunits. Contrary to expectation, the regulator enzymes of glycolysis; i.e., hexokinase, phosphofructokinase and pyruvate kinase were not included in this discriminant function. The best fit produced a 90% correct classification in both benign and malignant disease. If these findings are confirmed to a larger series, the discrimination is sufficiently strong to form the basis of a clinically useful tool.     

Compliance with screening mammography. Survey of primary care physicians

A survey of primary care physicians in the greater Tampa Bay metropolitan area was conducted to determine compliance with screening mammography and associated physician characteristics. Information requested included their age, sex, specialty, and board certification status, and the ages and frequencies that they recommend screening mammography for their patients. A total of 565 physicians responded. Even though 88% indicated they follow American Cancer Society recommendations when advising screening mammography, only 62% were actually in full compliance. A significantly greater percentage of obstetricians/gynecologists were compliant (74%) compared to other specialties (family practice, 57%, p = .006; internal medicine, 56%, p = .007; general practice, 53%, p = .003). Women physicians were more likely to be compliant than men (83% versus 58%, p less than .001), and younger physicians more likely than older physicians (72% versus 49%, p less than .001). There was no significant difference in compliance rates between board certified and noncertified physicians.     

Diagnostic role of MRI in localized cancer of the prostate

The authors extracted 11 case files of patients undergoing radical prostatectomy following MRI studies from a series of 192 MRI examinations of the prostate with histological confirmation of the diagnosis. This series is part of a prospective study in which MRI was always interpreted prior to histological results. The diagnosis of prostatic cancer was confirmed in 9 cases on the basis of a hyposignal on T2-weighted scans. In 4 cases, extracapsular spread of the tumour was demonstrated by MRI and was confirmed at surgery. In the cases in which the cancer was visible on MRI, the diagnosis of local spread proved to be accurate. The debate concerning the role of MRI in prostatic disease is not definitively resolved, but this preliminary series indicates the potential and the limitations of this technique.     

Neuromedin-induced excessive grooming/scratching behavior is suppressed by naloxone, neurotensin and a dopamine D1 receptor antagonist.

Neuromedin B and neuromedin C were tested for their grooming/scratching-inducing effects and the composition of neuromedin-induced grooming was established by calculating the relative contribution of various grooming elements to the total grooming scores. Excessive grooming induced by neuromedins is characterized by a predominant display of scratching. Since neuromedin C is much more potent than neuromedin B to induce excessive grooming/scratching behavior, it is concluded that the carboxyl-terminal heptapeptide of neuromedin C is important for this effect. Furthermore, it is concluded that dopamine D1 receptors and opiate receptors are involved in this effect since the dopamine D1 receptor antagonist, SCH 23390, as well as the opiate receptor antagonist, naloxone, suppresses or attenuates neuromedin C-induced excessive grooming/scratching behavior.     

Enhanced healing of 30 microns Gore-Tex PTFE microarterial prostheses by alcohol-pretreatment

Polytetrafluoroethylene (PTFE) microvascular prostheses with a fibril length of 30 microns were pretreated with alcohol (n = 18), implanted into the abdominal aorta of rats and were evaluated at 1 day (n = 3), 1 week (n = 3), 3 weeks (n = 6) and 6 weeks (n = 6) to determine whether alcohol-pretreatment might improve their healing. Untreated PTFE microvascular prostheses (n = 18) functioned as controls (all prostheses: length 10 mm, I.D. 1.5 mm). The alcohol-pretreated PTFE microarterial prostheses were initially completely filled and covered with clot and showed fast and complete healing within 6 weeks: endothelial cells and smooth muscle cells on the luminal surface, and the interstices filled with fibrous-like tissue. In contrast, the untreated PTFE prostheses were initially not filled or covered with clot and showed only healing near the anastomotic sites and scarce tissue ingrowth into the wall. These results demonstrate that alcohol-pretreatment improves the healing characteristics of PTFE microarterial prostheses with a fibril length of 30 microns. The alcohol-pretreatment renders the PTFE material more accessible to clot and subsequently to cells.