[Determination of the best amino acid input after orthotopic liver transplantation].

Ten-three patients were investigated during the early postoperative phase after orthotopic liver transplantation to assess the adequacy of the amino acid (AA) supply during both parenteral (days 1-5) and enteral (days 6-9) nutrition. Plasma AA profile was determined preoperatively, on day 4 and 5 during TPN and on day 8 and 9 during EN, urea production rate was measured every day. Calories input was 28 kcal.kg-.day as glucose, nitrogen intake was 0.25 g.kg- day, supplying individual AA on the basis of previous studies. Urea nitrogen production during TPN (9-11 gN/m2.day) outlines the ability of the transplanted liver to manage the overall nitrogen load. Individual AA plasma profile was considered the expression of an adequate input when comprised between 1 and 1.5 times the normal value, in this respect we obtained adequate levels of all essential AAs. Particularly phenylalanine, methionine and branched chain AA, critical during liver failure, were kept in this range by supplying 68, 48 and 500 mg.kg-1.day. According to AA profile the supply of cystine and tyrosine (conditionally essential AAs), and of histidine, taurine, proline and serine could be safely increased. Not given dispensable AAs (glutamine, asparagine, citrulline and alfa amino butyric) showed a plasma level below the norm and should be added to the diet.


[Problems related to resuscitation in studies with contrast media].

This study has the purpose of describing indications and legal implications related to the intravascular use of contrast media (ICM) in order to provide useful guidelines to the intensivist, often involved in the treatment of adverse reactions. The structure of modern contrast media (CM), is a benzenic ring carrying steadily three iodine ions. Adverse reactions due to the use of ICM, are local or systemic ranging from skin rashes or flushes (urticaria et al.), to cardiovascular, respiratory and neurologic symptoms. The prevention of these reactions is mandatory in patients reporting a history of allergy or atopia disease. From a legal point of view, the contraindication to procedures involving i.v. use of CM are not clearly pointed out therefore several concerns have been expressed. The intensivist is not required to physically attend the procedure, in agreement with the circular #64 edited in 1979; on the other hand his prompt intervention should be granted if necessary. Furthermore every therapeutic supply suitable for any resuscitational intervention should be available in the area where the test is performed. In conclusion we would like to stress the financial and ethic implications related to the choice of ICM (ionic versus non-ionic). The use of non-ionic CM offers several advantages: among them the better tolerance for the patient and the lower incidence of adverse reactions. However non-ionic CM have a cost ten-fold higher and both groups of drugs have same incidence of fatal reactions, therefore the use of non-ionic ICM is recommended for high risk patients.


[Sleep disorders in patients in recovery. Preliminary results in 20 patients].

Various aspects of the critically ill patient sharing pain, physical distress, anxiety, environmental components, predispose him to develop some sleep disorders (SD). We studied 20 conscious patients, age 16-80 (mean 48.15 SD of mean +/- 25), undergoing ICU mean 14.3 days (SD of mean +/- 7.5), to evaluate SD rate and their possible leading causes. Through Spearman Rank test SD was related to Apache II score, admission state anxiety, satisfactory sedation, days of ICU stay and age respectively. Conclusive results showed SD rate in all our patients. Excepted a statistical trend to significativity of SD versus satisfactory sedation: RS 0.311 (threshold value for 20 patients: 0.377), no relation was found between SD and data recorded. These preliminary results emphasize the importance of looking for SD in ICU patients though many factors may play a role to develop them.


[Neuropsychologic effects of anesthesia in the elderly].

Two anaesthetic techniques, the general balanced anaesthesia and the spinal one, have been compared in relation to their effects on neuropsychological functions as assessed by a neuropsychological test battery. Seventeen patients, who underwent different kinds of operations, have been kept under observation and checked up from a neuropsychological point of view 3 days before (time A) and 7 and 30 days after the operation (respectively time B and time C). No statistical significant differences in relation to the two anaesthetic techniques were found when comparing A, B and C assessment times. A decrease in cognitive performance at time B and a gradual return to basal condition were observed in patients who underwent general anaesthesia. Nevertheless the lack of statistical significance of the observed data leads to the need for further investigation.


[New duties for anesthetists in blood transfusion].

The Authors discuss new duties assigned to anaesthetist-resuscitators by Italian transfusional law (107/90, D.M. 27.12.90, Technical Directions). Preoperative hemodilution is the main task, and the need for the anaesthetist to perform it autonomously has important medical-legal consequences.


[The use of nefopam in the prophylaxis and treatment of postoperative shivering].

Chlorhydrate nefopam was used in the prophylaxis and treatment of postoperative shivering in 54 patients undergoing general anesthesia for radical cystectomy with trans-intestinal anastomosis. Postoperative shivering was not observed in any of the patients treated with nefopam before coming round, whereas it occurred in 55% of patients treated with placebo. Chlorhydrate nefopam subsequently stopped shivering in all these patients. The main side effects observed took the form of delayed awakening in 11% of patients receiving prophylactic treatment and somnolence lasting 5-10 minutes in all other patients.


[The use of propofol in status epilepticus].

Three cases of status epilepticus not responsive to an aggressive treatment are described. The seizures and EEG activity were rapidly brought under control with a continuous infusion of propofol (3-6 mg/kg/hour), maintained between 21 hours and 7 days. Patient awakening at the end of the infusion period was rapid and without sequelae.


[Resistance to non-depolarizing myorelaxants. Our experience with 3 clinical cases].

The Authors report their own experience in three patients that showed reduced sensitivity to atracurium or vecuronium. Two patients were affected by neoplastic diseases and one by hand trauma. Doses of 0.5 mg/kg of atracurium and 0.08 mg/kg of vecuronium were unable to establish a complete neuromuscular blockade. The Authors review the main clinical situations in which resistance to non-depolarizing muscle relaxants is known: burns, hepatic diseases, chronic therapy with anticonvulsant drugs. Possibly, such events are due to fast elimination of the drug, or to an increased number of acetylcholine nicotinic receptors, or to an unknown acutely acting circulating factor, or to increased binding of the drug to plasma proteins. Up to date, no well-established explanation is available.


[Hepatocystic ducts: anatomic curiosity or surgical challenge?].

The Authors report two cases of cysto-hepatic ducts. Clinical and therapeutic patterns of this rare biliary disease are stressed, underlining the surgical hazard related to iatrogenic damage of bile ducts during operative manoeuvres.


[Costo-clavicular outlet syndrome].

Syndromes caused by the compression of the neurovascular bundle are not a rare pathology, though their exact frequency cannot be assessed. Neurovascular bundle in the upper limbs may be compressed at the costo-clavicular space, interscalene triangle or at the insertion of the minor pectoralis muscle into the coracoid process. More than 90% of patients present neurological symptoms and 10% also have vascular problems. Diagnosis depends on a careful clinical and instrumental study of the patients. Arteriography, phlebography and Doppler tests were of value in the diagnostic approach, showing the compression of the subclavian artery and vein using the arm abduction manoeuvre. Electromyography is of value in differential diagnosis of the carpal tunnel syndrome showing the entity and site of nerve compression. The best form of surgical treatment is resection of the first rib according to Roos, using an extrapleural and transaxillary route.


[Leiomyoma associated with esophageal diverticulosis].

The Authors report a case of leiomyoma located in an epi-phrenic diverticulum. The development of the leiomyoma may have weakened the esophageal wall and caused the diverticulum to appear. Surgical treatment consisted of diverticulectomy with myotomy and a Belsey MK IV antireflux procedure.


[Local recurrence after gastrectomy for cancer. Presentation of 2 clinical cases].

The Authors report two cases with local recurrence after partial gastrectomy for advanced gastric carcinoma. The Authors suggest that chemo and/or radiotherapy associated with surgical treatment can improve the prognosis in some patients with recurrence. Response to chemotherapy and time elapsing before recurrence appears may select this group of patients.


[Peritonitis caused by jejunal perforation resulting from metastasis of pulmonary carcinoma].

The Authors report a case of peritonitis due to perforation of a single small bowel metastasis in a woman affected by right upper lobar lung carcinoma still with neck's lymphnodes and cerebellar metastasis. They underline the rarity of the finding and analyze its clinical, therapeutic, prognostic problems.


[Diverticulitis of the right colon. Presentation of a clinical case].

The recent observation of one case of diverticulitis of the right colon led to an evaluation of clinical diagnostic and therapeutic aspects of this comparatively rare condition, on the basis of reported data. Preoperative diagnosis is very difficult because it clinically resembles acute appendicitis in many ways, or because of the objective observation of a mass in the right iliac fossa. Instrumental examinations require preparation times that are often incompatible with the degree of surgical urgency. In the reported case, the inflammatory process was modest and treatment was straightforward, there being no diagnostic doubts. This confirms the fact that in so-called "usual" cases, the idea surgical approach must be as conservative as possible. In so-called "hidden" cases, on the other hand, the doubt as to the nature of the pathology often leads to extensive surgery, such as right hemicolectomy.


[Postoperative extrapleural pneumothorax. Presentation of a case].

The authors discuss a case of pneumomediastinum observed in the course of acute bronchitis and after an operation performed with general anesthesia and orotracheal intubation.


[Pseudocyst of the adrenal gland: diagnosis and treatment. Description of a clinical case].

A case of pseudocyst of the suprarenal gland in a 32-years-old woman is reported. Stress is laid on the description of the clinical case and the diagnostic and therapeutic problems involved are reviewed.


[A case of retroperitoneal leiomyosarcoma. Considerations].

A case of retroperitoneal leiomyosarcoma is reported. The retroperitoneal localization is quite unusual and early diagnosis is really difficult. Only operation can offer any chance for cure of this neoplasm and radiotherapy and chemotherapy can be very useful. Tumor size and location are the major prognostic factors.


[Primary malignant lymphoma of the parotid gland. Report of a case].

Primary malignant lymphoma of the parotid gland is often correlated, in literature data, with inflammatory autoimmunological disease of the salivary gland. Finding of blasticlymphoid cells in myoepithelial scialoadenitic areas in a case of parotid disease is described by the Authors. Needle may be useful in detecting these high radio-chemosensitive neoplasms to reduce the occurrence of complications of total parotidectomy.


[Choledocholithotomy and papillosphincterotomy in surgery of the bile ducts].

The Authors argue about the different surgical choices feasible in case of CBD stones. They consider a case-record of 74 patients that underwent, from January 1988 to June 1990, choledocholithotomy or transduodenal sphincterotomy for non-neoplastic pathology of the CBD in the I Divisione di Chirurgia Generale OO.RR. Bergamo. Analysis of the data shows a significant pre-operative alteration of the gamma-GT plasmatic levels. That represent a risk-index useful to suspect a silent CBD lithiasis. The good results attained with the choledocholithotomy and with the transduodenal sphincterotomy show the efficacy of both methods, that keep up different indications. The Authors point out the efficacy of the antibiotic prophylaxis in the prevention of the operative infections.


[Reconstruction of the abdominal wall for "major" hernia. Conventional methods vs the use of prosthesis].

The result of using traditional techniques in the treatment of large hernias of the abdominal wall (recurrent inguinal hernia and incisional hernia) are compared with those obtained by using prosthetic material. In most cases of incisional hernia the reconstruction was carried out by traditional techniques. Instead, the Authors' preference is for the use of prosthetic material in the treatment of recurrent inguinal hernia.


[Local and regional recurrence of cancer of the breast].

The Authors, through the study of their patients, and comparing it to other reports, help to further define the meaning, prognosis and type of treatment of local recurrences (LR) in breast cancer. They study 25 cases of LR after 238 operations on which regular clinical follow-up was carried out. They consider the various prognostic indicators for LR, the types of treatment and the results which are reached. Median survival after LR treatment was significantly better in patients N- (49 months vs 7 months in N+: p = 0.004). LR was more frequent when primary tumor was situated in inner quadrants; only 36% of their cases depend on primaries of the upper outer quadrant. An aggressive treatment (surgery, radiotherapy, chemotherapy) insures a better survival even if primary cancer is N+ greater than 3. The importance for prognosis of lymphnodal status is confirmed. Possible explanations are presented regarding the relatively lower incidence in upper outer quadrant cancers. An aggressive treatment of LR is suggested, specially when prognostic indicators are unfavourable: LR is very often a sign of systemic relapse of illness, particularly when it occurs after a short disease-free interval.


[The use of Sorbsan in the treatment of the donor site of skin transplantations].

Sorbsan is a new dressing composed of alginate fibers extracted from seaweed. It is claimed to have important hydrophilic, haemostatic and biocompatible qualities. Sorbsan was used in the treatment of the donor site of split skin grafts in 52 patients operated in this department from 1988 to 1990. The patients of this series required a skin graft for various reasons as detailed below: a) skin burns in 24 cases; 2) covering of a muscle flap used in the treatment of sacral pressure sores in 15 cases; c) 13 cases of loss of substance from other various causes. Healing time averaged 16.8-13.4 and 9.3 days respectively in the three groups reported above. In 85% of cases, healing was achieved in a period variable between one and two weeks and a half, varying in accordance with patient age and general conditions. The speed of healing, particularly where thin grafts were taken, allowed multiple split skin grafts to be taken from the same donor site, facilitating the treatment of extensive skin burns. The dressing can be removed with ease with only minimal discomfort to the patient. The incidence of side effects such as itching and scar hypertrophy or pigmentation is low. We haven't noticed any allergic reaction in this series. We found the use of this dressing satisfying in the treatment of donor sites of split skin grafts, particularly in terms of patient comfort and speed or healing.


[The application of microanastomoses in the surgical treatment of varicocele].

We operated on 50 patients with varicocele employing microsurgical anastomosis. Clinical results were satisfactory with varicocele disappearing 49 times out of 34 cases. The shunt between a high regimen pressure with a lower one improve the venous drainage of the testis. These new techniques must be selected according to the pathogenic mechanism of varicocele.


[Progressive pneumoperitoneum in the preparation for surgical intervention for voluminous ventral hernias].

The paper report three patients suffering from voluminous ventral hernias who were treated using progressive pneumoperitoneum as a preparative method prior to reparative surgery. On the basis of the results obtained, the authors sustain the rationality, safety and efficacy of the procedure, in particular given its ability to reestablish good respiratory and circulatory function in those cases where the latter were severely affected by hernia. Since this method needs a longer application time and therefore involves a greater economic burden, pneumoperitoneum should probably be reserved for selected cases, and alternative techniques should be used in patients where hernia is more easily resolved.


[MTBE perfusion via nasobiliary drainage followed by endoscopic lithotripsy in cases of complicated lithiasis of the common bile duct].

Pernasal catheter perfusion with MTBE and subsequent endoscopic lithotripsy is an effective treatment of complicated common bile duct lithiasis in which a first endoscopic attempt has failed. The authors analyzed their experience in 1990.


[Merkel's tumor. Some comments and the authors' personal cases].

The clinical features of 7 cases of primary neuroendocrine carcinoma of the skin (Merkel cell tumor) are reported. This cancer arises in the dermis and subcutaneous tissues of elderly individuals. Natural history is characterized by local recurrences (30%), regional lymph node metastases (65%) and distant metastases (40%). Surgery is the elective treatment, chemotherapy and radiotherapy resulted in only short-term palliative response.


[Carotid-subclavian bypass. Our experience with locoregional anesthesia].

Carotid-subclavian bypass has been adopted since 1956. The commonest indication is to abolish arterial occlusion or stenosis in patients with subclavian steal syndrome. Ten patients were submitted to carotid-subclavian bypass under regional anaesthesia: block of anterior rami of spinal nerves C3-C4 and block of cervico-brachial plexus by injection into the continuous perineural connective tissue space at the level of C6. The surgical procedure required carotid occlusion and cerebral function monitoring. The advantages of regional anaesthesia are the ability to monitor the patient's cerebral perfusion and function, to detect intraoperative ischaemia and embolisation and minimal interference with the cardiovascular and respiratory function.


[Acute diaphragmatic lesions due to closed thoracic-abdominal trauma].

Diaphragmatic injuries due to blunt trauma are steadily related to a high mortality. Their diagnosis may be difficult, due to the lack of specific symptoms and, more frequently to the high incidence of coexisting lesions which can mask the clinical appearance. This work presents the main aspects of ten cases admitted to the Emergency Surgery Division of Cagliari (USL 21), during the last seven years, with a review of the literature.


[Drainage of the pleural cavity].

The authors, from their personal experience, demonstrate the goals, the indications, the techniques and complications of performing a drain of the pleural cavity (DCP). DCP has an important role as a single operation or at the end of every thoracic operation. For this reason it is mandatory to respect the principles and the concepts reported by the authors.


["The difficult nose". Notes on the surgical technic in selected cases of septorhinoplasty].

The authors present a series of 20 patients who have undergone a complex septorhinoplasty. Its complexity is due to the presence of a serious deviation of the nasal septum, with an altered anatomy and position, and to the contemporaneous malformation of the nasal profile, laterally displaced in respect to the facial axis and with accentuated hump of the nasal bones. The aim of this presentation is to indicate the resolution of both problems with a single surgical operation.


[The prevention of DVT after general surgical interventions for cancer pathology].

The efficacy of postoperative DVT prophylaxis of defibrotide and heparin calcium was evaluated in a group of 47 patients undergoing general surgery for oncological pathologies. A sub-group (24 patients) received defibrotide treatment, 400 mg b.i.d. i.m.; the second subgroup (23 patients) was treated with heparin calcium, 5000 IU b.i.d. s.c., from the day before operation until the 7th postoperative day. No postoperative thrombotic symptoms were observed in either group of patients.


[Atypical metastases from gastric carcinoma. A primary and isolated case localized in the abdominal wall].

The authors report a rare case of gastric carcinoma metastasis localised in the anterior abdominal wall which was an isolated and primary sign of disease. After having underlined the rarity of the case, there is a brief discussion of aspects related to the spread of primary tumours in relation to other cases reported over the past decade; the most important reports of atypical secondary localisations are listed.


[A rare tumor: desmoid of the musculus rectus abdominis. Apropos a clinical case].

The authors report a case of left abdominal rectum muscle desmoid tumor which has been surgically treated. After some considerations of the particular pathogenetic, anatomopathological and clinical characteristics of this neoplasm, they state that a precise preoperative diagnosis is always difficult, in spite of modern diagnostic means. They conclude that, nowadays, surgical extirpation is the most reliable therapeutical method, although it is burdened by a consistent incidence of local recidives (over 30%).


[Extraskeletal myxoid chondrosarcoma of the abdominal wall. A clinical, histological, ultrastructural and cytofluorimetric case study].

The authors present a case of extraskeletal myxoid chondrosarcoma of the abdominal wall, an unusual localization and specific presentation. According to the literature, the clinical characters of this kind of tumor, the diagnostic iter and the therapeutic indications are being examined. The actual anatomopathological patterns used for the diagnosis of this neoplasm are being underlined.


[A case of transareolar mastocele (tuberous breast) following an early lateral thoracotomy].

The paper reports a rare case of breast anomaly, classified as "tuberous breast", which was of a specific nature since it was the result of a lateral thoracotomy performed at the age of 7 days old to esophageal atresia. The paper analyses the possible etiopathogenetic mechanisms. The use of an original reparative technique enable an adequately shaped and protruding breast to be obtained without the use of prosthesis and without leaving additional scars.


[Angioma of a finger: the usefulness of a graft from the hypothenar eminence for covering the defect].

Skin grafting remains the simplest option when bone is not exposed in soft tissue losses of the digits of the hand. As opposed to traditional donor sites, a split-thickness skin graft from the hypothenar eminence provides specialized skin similar to the one to be replaced. The graft remains elastic and soft in follow-up, without hyperpigmentation, hyperkeratosis, fissuring and hypertrophic scarring at the margins. As well as in acute trauma situations, the use of split-thickness skin grafting from the hypothenar eminence can also be extended to resurfacing defects in elective hand surgery. As an example, we describe a case of an ulcerated capillary hemangioma on the dorsal surface of the fifth digit at the distal interphalangeal joint.


[Transcutaneous oximetry in symptomatic diabetics].

In a group of 33 patients affected by diabetes mellitus transcutaneous oxygen tension (PtcO2) was measured by means of a Clark polarographic electrode. Patients were divided into 3 groups according to the symptoms and/or to the clinical findings: group A: paresthesia (22 limbs); group B: claudication (6 limbs); group C: rest pain and/or necrosis (13 limbs). Moreover, group C was divided into: C1 trophic neuropathy lesion (7 limbs) and C2 trophic ischemic lesion (6 limbs). Our data point out that there is a statistically significant difference between mean PtcO2 values in limbs with trophic ischemic lesions versus the other 3 groups. Therefore, PtcO2 is particularly indicated and useful in the study of diabetic patients with peripheral vascular disease where integrates the other instrumental noninvasive techniques.


[Nutrients, anthropometric characteristics and osteoporosis in women in the recent and late postmenopausal period].

Bone mineral content (BMC) at two different radial sites (mid-diaphysis and ultra-distal epiphysis), anthropometric measurements (Body Mass Index, Lipidic Area, and Muscular Area) and nutrients intake were measured in two populations of women selected on the basis of early (< 9 years) or remote (> 15 years) menopause. The results show the presence of positive relationships between BMC, and protein and lipid intakes in the population of women in early menopause; in the other population no relationships were found. Glucid, fibre and calcium intakes were not related to the BMC of both populations. The positive relationships between BMC, and protein and lipid intakes in the population of women in early menopause is likely mediated by anthropometric characteristics as Body Mass Index and Muscular Area.


[Zymogenic cell mass and serum pepsinogen I: the cell secretory correlations in patients with gastric intestinal-type cancer of the corpus-fundus].

The chief cell mass and serum pepsinogen I (PGI) have been evaluated in 18 patients with gastric cancer of intestinal type of the body-fundus. Moreover, a correlation with the parietal cell mass and the maximal acid output it has been effected. The patients have been subdivided in relation to histologic condition of the fundic mucosa. In case of gastric cancer with preatrophic fundic gastritis it has been revealed hypozymogenism with normoPGI and hypoparietalism with hypochlorhydria, in case of gastric cancer with atrophic fundic gastritis it has been revealed hypozymogenism with hypoPGI and hypoparietalism with hypochlorhydria. From this experience it emerges a similar anatomic-functional profile between gastric cancer of the body-fundus and chronic fundic gastritis without cancer. In particular, it emerges that serum PGI is a good marker of atrophic fundic gastritis, but it is not discriminant between atrophic fundic gastritis and atrophic fundic gastritis associated to gastric cancer.


[Transient cerebral ischemia and the risk factors].

A retrospective study was carried out in a general medicine ward of 100 male patients suffering from their first transient ischemic attack (TIA) in order to evaluate the incidence of different cerebrovascular risk factors. The results were then compared with those from another group of 100 patients suffering from initial cerebral ischemic softening (CIS) in order to identify a cerebrovascular risk population taking into account clinical similarities and common and divergent features. The study revealed that age is the prime risk factor in the genesis of TIA, followed by arterial hypertension and hypercholesterolemia. From a comparison with the group of patients affected by initial CIS it was clear that TIA is typical of senility and is more closer correlated to age than other risk factors; therefore, che TIA population is an expression of those who have "survived" cerebrovascular death due to the lesser exposure to risk factors.


[Ticlopidine and platelet function].

In macular degeneration disease of the eye, we have studied the behaviour of vitro thrombocyte aggregation/deaggregation and ex vivo plasma beta-thromboglobulin level (Born aggregometer, RIA kit) during administration of an antiaggregant platelet drug (ticlopidine). We have observed the presence of a prothrombotic state that improves after 15 days of administration of drug. In fact platelet aggregation and beta-thromboglobulin level significantly decrease while thrombocyte deaggregation significantly increase. The correlations between deaggregation, aggregation and beta-thromboglobulin level suggest that the antiaggregant action of the ticlopidine is linked to the inhibition of platelet release reaction.


[The possible effects of galactosaminoglucuronoglycan sulfate on blood coagulation processes].

Ten patients with osteoarthritis were treated in an open study with galactosaminoglucuronoglycan sulphate for 60 days (800 mg b.i.d. per os). The following haemostatic indices were measured before and after treatment: platelet count, adhesion and aggregation; prothrombin time and activity; partial thromboplastin time and antithrombin III. Total and HDL cholesterolemia, triglycerides, arterial pressure and heart rate were also measured. No blood coagulation index was found to be significantly altered in treated patients. In addition, neither variations from the normal limits of lipidemic and cardiocirculatory values nor adverse effects related to treatment were reported. Although the study was carried out in a limited population, these findings show that GGG does not interfere with the coagulation process and, from a more general point of view, they confirm its excellent tolerance.


[Heparan sulfate: its kinetic effects on fibrinolytic-coagulative parameters after oral administration].

The effects of the oral administration of 100 or 200 mg of heparan sulphate or placebo over time were assessed in nine healthy volunteers. Blood samples were collected at 1, 2, 4, 6, 8 and 12 hours after administration to assay prothrombin activity, partially activated thromboplastin time, and the activation to tPA and PAI-1. A significant increase (P < 0.001) of tPA activity and a reduced inhibition of fibrinolytic systems by PAI-1 were observed. These effects, which were clearly dose-dependent, appeared 2 hours after administration and persisted for 6-8 hours. On the contrary, no changes were recorded in coagulative tests at the doses used.


[Ursodeoxycholic hemisuccinate in the treatment of chronic active hepatitis. A controlled clinico-therapeutic study].

This controlled study was performed on 36 patients affected by HBV and/or HCV correlated chronic hepatitis (CAH). Eighteen of them received 300 mg of UDCA-hemisuccinate orally twice a day for six months; the other 18 received 200 mg of S-adenosyl-methionine (SAMe) twice a day for six months. The two groups were determined randomly. Treatment with UDCA-hemi-succinate produced a statistically significant reduction in ALT (from 167 +/- 17 to 119 +/- 15 U/l; p < 0.0001), AST (from 122 +/- 14 to 86 +/- 11 U/l; p < 0.0001) and y-GT (from 81 +/- 10 to 53 +/- 6 U/l, p < 0.0001). The results obtained suggest that UDCA-hemi-succinate may be useful in the long-term treatment of chronic liver diseases of viral aetiology because it improves the biochemical parameters of hepatocellular necrosis and/or increased liver cell permeability.


[The use of thymopentin in preventing acute infectious relapses in elderly subjects with COPD].

In this study the authors considered the effectiveness of thymus hormone in the prevention of acute infections within a group of elderly subjects affected by COPD. Ten subjects were considered, nine males and one female in the age included between 65 and 89 years (medium age = 70.2 +/- 6.96 years), with clinical evaluation and altered functional respiratory tests (FEV1 < 70%). The patients were treated with timopentina 50 mg s c three times a week for a month. The following parameters were considered: leucocytes/mm3; lymphocytes/mm3 in standard conditions, in the first and in the second month after the therapy start, contagious episodes two months before and two months after the beginning of therapy. The Authors noticed a real reduction in the relapses of the infectious episodes (11 relapses in the months before therapy and 2 relapses after therapy had begun). Leucocytes/mm3 rates were reduced (8.070 +/- 3.414 in standard conditions, 6.420 +/- 1.041 after 60 days; 0.2 < P < 0.1). Lymphocytes/mm3 rates were increased, 1.579 +/- 752 in standard conditions, 2103 +/- 491 after 60 days 0.2 < P < 0.1). These preliminary data seem to show in the small number of cases considered, the effectiveness of the thymus hormone (thymopentina) in elderly subjects affected by COPD.


[Why a gynecological consultation service in a hematology day hospital. Our experience].

The paper described the role of a gynaecological advisory service in an hematological day hospital. The main gynaecological problems which arose during anti-cancer and immunosuppressive therapy were classified according to patients' symptoms. The paper stresses the need for close collaboration between hematologists and gynaecologists and underlines the psychological importance of this aspect from the patient's point of view.


[Systemic mastocytosis with portal hypertension and hepatocellular failure].

Systemic mastocytosis is a rare disease of mast cell proliferation with cutaneous and multi-visceral involvement. Portal hypertension and ascites are rare manifestations of systemic mastocytosis. We report a case of systemic mastocytosis presenting with extensive nodular cutaneous lesions and hepatic dysfunction, manifested by portal hypertension (ascites, splenomegaly) and derangement of metabolic function (hyperammonemia, hypoalbuminemia, hypocholesterolemia), a picture resembling that of a common cirrhotic form. The correct diagnosis was established only after tissue sections were appropriately stained for mast cells. On the basis of our and other observations we suggest that systemic mastocytosis be added to the list of infiltrative diseases of the liver with potential evolution to portal hypertension and compromise of biochemical functions.


[Ischemic colitis manifested as Crohn's disease. A case report].

Ischaemic colitis has many and different clinical features as it is often linked to the severity of ischaemic injury. In this paper two patients with clinical features of Crohn's disease are reported. In both patients the diagnosis has been confirmed with endoscopy and biopsy. They have been treated with specific therapy until they developed bowel obstruction in one case and peritonitis in the other. Both patients underwent laparotomy and the histological specimen showed a picture of ischaemic colitis. In one case a Dixon's resection was done, in the other Hartmann's operation.


[The infusion of high-dose immunoglobulins in a case of idiopathic thrombocytopenic purpura].

Idiopathic thrombocytopenic purpura (ITP) is a disease characterized by the presence of circulating antiplatelet antibodies, which can cause platelet destruction, through the mediation of the reticuloendothelial system (RES). We report on a patient affected with ITP insensible to first line steroid therapy, who achieved a complete response following the administration of high-dose immunoglobulins (HDIgG, 400 mg/kg/die for 5 days), in association with decreasing doses of steroids. At the end of the treatment with immunoglobulins, the patient presented a normal platelet count and, up to date, 5 moths from the end of therapy, he is in good shape and presents normal platelets values.


[Unilateral gynecomastia induced by the use of anabolic steroids. A clinical case report].

The authors studied a case of left unilateral gynecomastia occurring in a 26-year-old body-builder after anabolic steroids assumption. The mammal features were found by echography and mammography and they showed the presence of a 3 cm diameter retroareolar area of gland tissue surrounded by fibrotic tissue. After excluding every likely cause giving gynecomastia through laboratory tests, it was clear a relationship with the assumption of high doses of anabolic hormones, with particular regard to methyltestosterone. Therefore, also this substance which on its own is not aromatized by extrasplanchnic tissues, can be responsible for man's mammal hypertrophy, if joined to a slight iatrogenic liver cytolysis.


[Non-sexual transmission of sexually transmissible diseases].

Sexually transmitted diseases can be transmitted through nonsexual transmission. Neonatal contamination has been proven at parturition from mothers with anogenital diseases. Another example is transmission through exchange of underwear, towels, bed sharing, etc. It is possible that contamination may occur with use of the contaminated speculum and forceps. Use of laser may release viruses during treatment for viral diseases. Candidiasis, trichomoniasis and genitalis condilomatosis, which should not be considered an exclusively sexually transmitted diseases are considered.


[Synchronous associations of tumors in the pelvic organs of the female genital tract].

The Authors report their findings concerning the synchronous associations of tumours involving pelvic organs in the female genital tract observed at the Gynecological Clinic, Aquila. From January 1980 to December 1991, 9 cases (4.28%) of synchronous tumours were found in a total of 210 cases of womb, ovary and vagina tumours. The paper examines the clinical problems and questions of anatomopathological characterisation raised by these associations.


[Clinical evaluation of an immunological test for premature rupture of the fetal membranes (ROM check test)].

Commonly used methods for detecting amniotic fluid in the vagina include research LA cells, ferning, nitrazina paper, ultrasound and dye injection. These methods are difficult to interpret or invasive. We have tested a new method which detects a fetal isoform of fibronectin in vaginal secretion when amniotic fluid is present. Clinical trials demonstrate the sufficient reliability in detecting amniotic fluid in the vagina of women with rupture of amniotic membranes.


[Collagenase IV and laminin receptors in cultured trophoblast cells].

Human trophoblast cells were obtained from a term placenta and cultured through several stages. Using specific antibodies marked using an avidin biotin system and given the characteristic "invasiveness" of placental tissue, the Authors investigated the possible presence of those markers which have been found to be correlated with invasive and metastatic tumour cells. The positivity shown by cultured trophoblast cells towards laminin receptors and collagenase IV may have important implications which might explain the strange formation and maintenance of the human uteroplacental circulation in which embryonal tissue is in direct contact with maternal blood.


[Hysteroscopy as a diagnostic method in postmenopausal metrorrhagia].

We performed 215 hysteroscopies for post-menopausal bleeding. The most common abnormalities found were endometrial hypoatrophy and low-risk hyperplasia, the less common high-risk hyperplasia and adenocarcinoma of the endometrium. The correlation between hysteroscopic view and endometrial sampling was always very high. Hysteroscopy seems to be a very accurate method for evaluating patients with post-menopausal bleeding especially if associated with endometrial sampling.


[Radiologic types in mammography in the 90-s. New classification].

The Authors present a critical review of the classification of radiological types in mammography proposed in 1986. On the basis of their personal experience over the past years, and in the light of the changed indications given by screening the asymptomatic population, a series of 6,072 mammographies performed over a 12-month period were included in the study. These were non-selected cases undergoing X-ray examination for a variety of reasons, ranging from periodical control to carcinophobia. No clinical or epidemiological data were taken into account in order to limit analysis to radiological factors alone. The analysis of results allows a few comments to be made and suggests an interpretation which differs from that in vogue in the 80s. First of all, the steady rise in mammographic controls calls for an uniformity of technique with interchanges of information between the various centres of breast cancer in order to encourage increasingly accurate diagnostic evaluations. The higher incidence of the trabecular type (33.7%), typical of women in their 40s, underlines the greater diffusion of mammography which now starts at an increasingly early age. Current control programmes (in spite of some recent controversy) include 40-year-old women who undergo basic mammography in spite of the absence of symptoms. On the other hand, the irreplaceable diagnostic value of mammography during the asymptomatic years is now widely recognised, even in those women who undergo a regular clinical examination. The fibroadipose type has dropped to second place (26.8%) not due to a reduction in the number of these cases, but rather on account of the lower age at which women first undergo mammography.(ABSTRACT TRUNCATED AT 250 WORDS)


[Sampling devices for the Papanicolaou test].

Smear quality is related to the experience of the sample taker and also to the screening instrument used. Most Authors concur that both an endocervical and an ectocervical specimen must be collected to assure adequate sampling of the transitional zone. The cytobrush alone is effective mainly for endocervical sampling while the Ayre spatula alone is effective mainly for ectocervical sampling; the cotton swab is ineffective for both endocervical and ectocervical sampling. Values and failure of the sampling devices are described.


[Obstetric-gynecologic problems in the developing countries].

The integrated health programmes in the developing countries give priority to the improvement of women's living conditions and of maternal and child health medical attention. The Authors, as specialists in Obstetrics and Gynecology active in an African country, present the most frequent pathological situations which, in their experience, can lead to the death of the pregnant woman. The social reality of the underdeveloped world and the high Total Fertility rates, due partly to the absence of a contraceptive culture, too often see the woman of reproductive age threatened by the complication deriving from abortion, ectopic pregnancy and labour. The obstetrician needs to know how to solve these emergencies and how to train the local personnel in order to guarantee as much as he can the essential obstetrical functions.


[Cervico-vaginal screening in some Local Sanitary Units of the Emilia-Romagna region].

Some Local Sanitary Units (USL) of the Emilia-Romagna region were contacted to define cervical screening variables, such as adequacy of smear technique, data collection and evaluation, laboratory quality control modalities of invitations to screening. Our data show there are a lot of deficiencies in the present management of the cervical program in Romagna. The most serious inadequacies concern data evaluation, follow-up, cytologic quality control, modalities of active invitations of women to screening. The survey has confirmed the need for launching organized programs of cervical screening to promote their efficacy of diagnosis and therapy.


[Brenner tumor of the ovary. Report of a case in a pregnant women].

The Authors, after a short review on the histopathological, histogenetic and prognostic aspects, report a clinical case observed by them, in a pregnant woman. They emphasize the asymptomatic obstetric course and the accidental discovery during surgical treatment.


Murine BC1 RNA in dendritic fields of the retinal inner plexiform layer.

Rodent BC1 RNA is a non-messenger RNA polymerase III transcript that is almost exclusively expressed in nerve cells. BC1 RNA has been localised in somatic and dendritic domains of neurons, and its location has been interpreted to indicate a functional role in extrasomatic postsynaptic protein synthesis. In previous in situ hybridisation experiments, it has been demonstrated that in the retina most of the BC1 labelling signal was confined to the ganglion cell layer and the inner plexiform layer. Dendritic processes of several types of neurons form the neuritic plexus of the inner plexiform layer, and in order to determine the contribution of ganglion cells to the BC1 labelling signal, we eliminated this cell type by transecting the optic nerve unilaterally in newborn mice. Deletion of the ganglion cells resulted in a significant reduction although not a complete elimination of the BC1 signal in the inner plexiform layer. These data indicate that dendritic processes of both ganglion cells and amacrine cells contain BC1 RNA.


Histological study on ouabain immunoreactivities in the mammalian hypothalamus.

The endogenous digitalis-like factor (EDLF) which has recently been purified from human plasma and identified as 'ouabain', a cis-trans-cis steroid of plant origin, is thought to be similar to the hypothetical humoral factor, 'endogenous digitalis-like substance (EDLS)'. In order to examine the hypothesis that EDLS is produced in the hypothalamus, we prepared an ouabain-specific antibody, and applied it to rat and macaque brains. Ouabain immunoreactivities were observed in the hypothalamus of both species. The immunopositive neurons were distributed in paraventricular and supraoptic nuclei, and some other hypothalamic regions. Their nerve fibers were seen abundantly in the hypothalamo-neurohypophysial regions. These results strongly support the possibility of existence of cis-trans-cis steroid including EDLF in mammalian brain.


Inhibitory effects of endothelin-3 on vasopressin release from rat supraoptic nucleus in vitro.

Endothelin (ET) is thought to be involved in the central regulation of body water metabolism. A recent perfusion study of rat hypothalamus showed that ET has a direct stimulatory action on arginine-vasopressin (AVP) release. This study was undertaken to investigate whether ET acts directly on AVP release for supraoptic nucleus (SON) neurons, using brain slices containing only the SON. It was demonstrated that ET inhibited the AVP release dose-dependently from 10(-11) M to 10(-6) M. No difference of the effects of ET-1 and ET-3 on AVP release was observed. These results suggest that ET directly inhibits SON neurons through the ETB receptor.


Y-29794--a non-peptide prolyl endopeptidase inhibitor that can penetrate into the brain.

A novel non-peptide prolyl endopeptidase (PPCE) inhibitor, Y-29794, has been identified. Y-29794 selectively and competitively inhibited rat brain PPCE (Ki = 0.95 nM) in a reversible manner. Ex vivo study demonstrated that Y-29794 could penetrate into brain to exhibit dose-dependent and long-lasting inhibition. Furthermore, Y-29794 was found to potentiate the effect of TRH on the release of ACh in the rat hippocampus. These results indicate that Y-29794 is an orally active, potent and specific PPCE inhibitor and should be of value in studies on the physiological role of the enzyme in neuropeptide metabolism especially in memory process.


Protective effect of NGF atelocollagen mini-pellet on the hippocampal delayed neuronal death in gerbils.

Very recently, contradictory results were presented as to the effects of exogenous nerve growth factor (NGF) on the hippocampal delayed neuronal necrosis following transient ischemia. In the present study, we administered a large amount of NGF with the atelocollagen mini-pellet system, measured the local NGF contents, and evaluated the effect of this neurotrophic factor on the postischemic hippocampal pyramidal cells in gerbils. We concluded that the exogenous NGF, when given continuously at sufficient concentrations, prevents pyramidal cell damage. The possible cause of discrepancy in previous studies is discussed.


Time-dependent effects of oral morphine on autotomy following brachial nerve section in the rat.

In this study, the effects of morphine in drinking water on autotomy in male F344 rats having undergone brachial nerve sections were assessed during a 3-week period. Morphine was self-administered orally in tap water by the rats. Rats administered morphine just after the nerve section or 1 week after the nerve section showed a significant increase in the severity of autotomy when compared to the rats administered distilled water. Morphine had no effect on autotomy when it was administered 2 weeks after the nerve section. These results suggested that the effect of oral morphine on autotomy changes in a time-dependent manner.


Vasodilator flare due to activation of superficial cutaneous afferents in humans: heat-sensitive versus histamine-sensitive fibers.

Histamine-sensitive nerve endings are assumed to terminate in the superficial epidermis. Heat-sensitive nociceptors that are excited by brief carbondioxide-laser pulses must also terminate within the epidermis, because this infrared radiation has an extinction length of about 10 microns. We now compared laser heat stimuli (10 W, 50 ms, 20 mm2) with intradermal injections of histamine (10(-10) to 10(-8) mol) in their capacity to cause cutaneous vasodilatation (flare) in awake human subjects. Cutaneous blood flow was measured with a two-channel laser-Doppler device. The radiant heat pulses caused a transient cutaneous vasodilatation that spread at least 15 mm from the stimulus site. There was no visible flare and vasodilatation could only be detected by laser Doppler measurements. Although the heat pulses elicited enough nociceptor activity to be perceived as moderately painful, the magnitude of the vasodilatation was smaller and its duration shorter than after the smallest dose of histamine. In contrast, nociceptor activation by heat is usually stronger than by histamine. These data indicate that flare and pain are two different aspects of cutaneous small fiber function.


Spontaneous hemorrhage in the cerebral cortex of immature rats.

We report the presence of spontaneous hemorrhages in the brain of normal neonatal rats. The quantitative evaluation showed that the hemorrhaging was most frequent in 4- to 5-day-old rats. Nearly all the lesions were found in the cerebral cortex of the lateral part of the forebrain hemisphere, particularly in the middle cortical layers. Their average incidence amounted to 6.71 +/- 2.95 per six 5-microns sections from 5-day-old rats. The lesions were nearly absent in the newborn and 7-day-old animals. We suggest that vascular wall immaturity and some extravascular factors, like developmental increase of blood pressure, may account for the perinatal hemorrhaging.


Partial protective effect of MK-801 on MPTP-induced reduction of striatal dopamine in mice.

The protective effect of MK-801, an N-methyl-D-aspartate (NMDA) receptor antagonist on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced reduction of striatal dopamine (DA) was examined in C57 BL/6 mice. Striatal DA levels were significantly higher in animals receiving parenteral MK-801 before and for 48 h following MPTP administration after 28 days than in animals receiving MPTP alone. The effect was not due to inhibition of monoamine oxidase-B (MAO-B) by MK-801. These data suggest that NMDA receptors may be involved in some of the neurotoxicity produced by MPTP.


Nilvadipine as a neuroprotective calcium entry blocker in a rat model of global cerebral ischemia. A comparative study with nicardipine hydrochloride.

The effects of two dihydropyridine type calcium entry blockers, nilvadipine and nicardipine hydrochloride (nicardipine), on the liberation of free fatty acids (FFAs) were investigated using an experimental model of global cerebral ischemia in rats, and were compared with their pharmacokinetic properties. Nilvadipine, but not nicardipine, at a dose of 100 micrograms/kg i.v., significantly attenuated the liberation of FFAs, particularly docosahexaenoic and arachidonic acid. Furthermore, the brain concentration of nilvadipine was higher than that of nicardipine after equivalent dosing. The results of the present study demonstrate that pharmacokinetic differences between these two calcium entry blockers might explain the difference in their pharmacological efficacy.


Neurochemical lesioning in the rat brain with iontophoretic injection of the 1-methyl-4-phenylpyridinium ion (MPP+).

Iontophoretic injections of the 1-methyl-4-phenylpyridinium ion (MPP+) were made in the dopaminergic part of the substantia nigra to see whether this injection technique could be used for inducing localized neurochemical lesions in dopaminergic cell groups and to assess the effects of MPP+ on non-dopaminergic neurons. Three days after the iontophoretic injection of MPP+, a gliosis or necrotic hole was found in the dopaminergic and non-dopaminergic target areas. This effect depended on the injection parameters that were used; iontophoretic injections of short duration (less than or equal to 3 minutes) and low current strength (1.5 microA) caused the gliosis, higher injection parameters gave lesions. The estimated injected amount of MPP+ was between 0.5 and 10.8 nmol. Control injections, with sodium iodide, sodium chloride or N-methylpyridinium iodide showed that the neurodegeneration is not a side-effect of the iontophoretic injection procedure. It is concluded that iontophoretically injected MPP+ is toxic for all neurons, irrespective of the neurotransmitter used, and also for glia cells and fibers of passage. Excessive formation of free radicals, causing induction of lipid peroxidation, may be involved in the neurodegenerative process observed.


Lack of evidence for coupling of the dopamine D2 receptor to an adenosine triphosphate-sensitive potassium (ATP-K+) channel in dopaminergic neurones of the rat substantia nigra.

Whole-cell patch clamp recordings were made from neurones in slices of rat substantia nigra zona compacta. The majority exhibited electrophysiological characteristics seen previously with intracellular recordings and were hyperpolarised by dopamine in a sulpiride-reversible manner. The sulphonylureas, tolbutamide and glibenclamide, did not reverse the response to dopamine and had no effect when applied alone. The potassium channel opener, cromakalim, was also without effect on dopaminergic neurones. Under our recording conditions, the potassium conductance activated by dopamine acting through the D2 receptor does not show the pharmacological characteristics of an ATP-sensitive potassium conductance.


Reinnervation of denervated extensor digitorum longus of the rat by the nerve of the soleus does not induce the type I myosin synthesis directly but through a sequential transition of type II myosin isoforms.

The fast-contracting extensor digitorum longus (EDL) muscle of 1-month-old rats was denervated and reinnervated by the nerve innervating the slow-contracting soleus muscle. After variable periods of time, the myosin isoform content of the EDL was analyzed by sensitive electrophoretic techniques, which allowed to discriminate between the slow-type I and the three, IIA, (IID or IIX) and IIB, fast-type II myosin isoforms. Compared to the control EDL, which contains predominantly the IIB isoform, the operated muscles contained variable proportions of all the isoforms. Analysis of the results leads us to conclude that reinnervation of EDL induces a sequential transition of myosin isoforms: IIB----(IID or IIX)----IIA----I.


Effects of exogenous GM1 ganglioside on LTP in rat hippocampal slices perfused with different concentrations of calcium.

Combined actions of GM1 ganglioside molecules and Ca2+ ions on long-term potentiation (LTP) of the hippocampal CA1 synapses were examined in slice preparations. Application of exogenous GM1 ganglioside significantly enhanced LTP. Antigenic blocking of endogenous GM1 ganglioside by applying anti-GM1 antiserum appeared to attenuate LTP. Exogenous GM1 treatment not only antagonized LTP suppression caused by low Ca2+ (1.0 microM) in the perfusion medium, but also amplified LTP at high Ca2+ (5.0 microM) condition. Thus, GM1 may stabilize intracellular calcium levels to enhance synaptic potentiation.


Dual capsaicin-sensitive afferent pathways mediate inhibition of gastric emptying in rat induced by intestinal carbohydrate.

The role of the vagal and spinal afferent innervation in the inhibition of gastric emptying induced by duodenal perfusion with a disaccharide (maltose 300 mM) was investigated in awake rats fitted with gastric and duodenal cannulas. Perfusion of the duodenum with maltose inhibited gastric emptying by 44%. Maltose-induced inhibition of gastric emptying was reversed by 46% and 100% by functional ablation of the vagal or spinal capsaicin-sensitive afferent innervation, respectively. Pretreatment with the specific CCK 'A' receptor antagonist, MK329, completely abolished the effects of maltose on gastric emptying. These results suggest that disaccharides inhibit gastric emptying via activation of capsaicin-sensitive afferents in the duodenal mucosa via a mechanism involving an action of CCK at type 'A' receptors, possibly located on afferent fibers.


Tris inhibits (+)-[3H]SKF-10,047 binding to sigma receptors.

Tris-HCl is the most commonly used buffer in studies of radioligand binding to sigma receptors, with concentrations as high as 50 or 100 mM often used. We report here that these concentrations of Tris substantially inhibit (+)-[3H]SKF-10,047 binding to sigma receptors. The well-established inhibitory effect of Tris-HCl on ligand binding to PCP receptors did not contribute to the presently reported inhibition of (+)-[3H]SKF-10,047 binding. The IC50 of Tris, determined in the presence of 10 mM potassium phosphate buffer, was 15.4 +/- 1.2 mM (n = 3, pH 8.0, 25 degrees C, 1 nM radioligand). Equilibrium saturation studies revealed an apparent competitive inhibition of binding.


Methionine enkephalin accumulates in plasma but not in brain or cerebrospinal fluid of rats with acute toxic hepatitis.

In order to determine whether acute toxic hepatitis in the rat is associated with an accumulation of methionine enkephalin in plasma and increased blood-to-brain transfer of methionine enkephalin, immunoreactive methionine enkephalin levels were determined by radioimmunoassay in plasma, cerebrospinal fluid and whole brain samples from rats with thioacetamide induced acute toxic hepatitis. Thioacetamide treatment was associated with an 8.7-fold increase in plasma immunoreactive methionine enkephalin levels (P less than or equal to 0.005) 24 h after treatment. However, this marked elevation in plasma immunoreactive methionine enkephalin levels was not associated with an increase in whole brain or cerebrospinal fluid immunoreactive methionine enkephalin levels. These data suggest that increased plasma-to-brain transfer of methionine enkephalin does not occur in this model of acute toxic hepatitis.


The A2-selective adenosine analog, CGS 21680, depresses locomotor activity but does not block amygdala kindled seizures in rats.

The actions of the highly selective A2 adenosine agonist, CGS 21680, in modulating kindled seizures and locomotor activity were examined. I.c.v. injections of CGS 21680 into the lateral cerebral ventricle in fully kindled rats were found to prolong the period of postictal EEG depression and reduce postictal spiking in a dose-dependent manner, while not affecting the behavioral seizure stage or afterdischarge duration. CGS 21680 injections also lead to a dose-related inhibition of locomotor activity in rats exposed to an open field apparatus compared to rats receiving control injections of saline. These observations implicate the involvement of the A2 adenosine receptor in postictal phenomena and the locomotor depressant actions of adenosine, but do not indicate a direct anticonvulsant activity following A2 activation.


Intracortical grafts of purified astrocytes ameliorate memory deficits in rat induced by chronic treatment with ethanol.

Chronic intake of ethanol in rat results in a substantial and permanent impairment in memory function which can be ameliorated by intracortical grafting of fetal tissue derived from the primordial basal forebrain. The present study demonstrates that grafting of purified astrocytes is equally effective in improving the performance in the eight-arm radial maze. In comparison, the rate of behavioral recovery is even more accelerated after grafting of astrocytes than after fetal basal forebrain transplants. The improvement in memory function can be detected as early as 2 weeks after operation and is accompanied by an increase in the activity of choline acetyltransferase in the basal forebrain previously reduced after ethanol treatment. Graft-induced behavioral recovery in the present paradigm is most likely due to a neurotrophic influence of astrocytes mediated via the cholinergic basal forebrain system.


Unilateral hippocampal lesions prevent recall of a passive avoidance task in day-old chicks.

The role of the hippocampal system in learning and memory processes in the chick was investigated. A series of experiments examined the effects of lesions in the hippocampal system on the acquisition and retention of a passive avoidance task. Chicks given pretraining bilateral hippocampal lesions showed a decrease of retention of the avoidance response evaluated 3 h posttraining. When given unilaterally, left, but not right lesions, resulted in reduced avoidance. However, bilateral posttraining lesions, made 1 h after training, did not interfere with retention of the task. These results suggest an involvement of the hippocampal system in learning processes in the chick.


Differences in the axon composition of nerves supplying the rat knee joint following intra-articular injection of capsaicin.

This study was used to examine the ultrastructure of articular nerves supplying the medial aspect of the rat knee joint following injection of capsaicin into the synovial cavity. One week after the intra-articular injection of 0.2 ml of 1% capsaicin solution there was significant reduction in the number of unmyelinated fibres. Two weeks post-injection this appeared to recover and by 4 weeks post-injection no further changes were observed. Myelinated fibres were unaffected by capsaicin injection. This procedure provides an effective means of producing short-term degeneration of unmyelinated fibres innervating the knee joint.


Development of long-term potentiation in the somatosensory cortex of rats of different ages.

The age dependence of possible long-term potentiation (LTP) induction in rat somatosensory cortex was studied in in vitro slice experiments. Coronal slices were prepared from the somatosensory cortex of rats of different ages, and excitatory postsynaptic potentials evoked by stimulation of the white matter (0.1 Hz, subthreshold for spike) were recorded intracellularly. In 70% of the slices taken from 2-week-old rats, a moderate potentiation (20-30%) could be induced by either 5 or 100 Hz stimulation. No LTP was observed in younger (1 week) or older (3 weeks) cortex. On the basis of our experiments an important ontogenetic role of increased synaptic efficacy is suggested in a critical developmental period of rats after birth.


The excitation site of the trigeminal nerve to transcranial magnetic stimulation varies and lies proximal or distal to the foramen ovale: an intraoperative electrophysiological study in man.

The excitation site of the trigeminal nerve using transcranial magnetic stimulation (magStim) was analyzed in 5 patients in whom the trigeminal nerve was surgically exposed in the posterior fossa during microvascular decompression of the facial nerve for hemifacial spasm. The trigeminal nerve was stimulated (1) magnetically immediately prior to craniotomy, and (2) electrically near the root exit zone (elREZ) of the nerve from the brainstem. Mean latency differences (delta) of masseter compound muscle action potentials (CMAPs) (delta elREZ minus magStim) were 0.7 (range: +0.3 to +1.3) ms (P less than or equal to 0.05, Wilcoxon-test). From these results, an analysis of anatomical data, and using a trigeminal nerve conduction velocity (NCV) of 50 m/s as reported in the literature, the following conclusions were drawn: the excitation site to magStim (1) is variable among individuals, (2) is located 3.4 (1.6-6.5) cm distal to the trigeminal REZ, and (3) which corresponds to segments of the nerve that are located either within or outside the cerebrospinal fluid (CSF), either proximal or distal to the foramen ovale. These findings are in contrast to those we obtained in a previous study of the facial nerve in which the excitation site was found to be constant among subjects and restricted to the location on the nerve where it exists the high conductivity CSF to enter the high-resistance petrous bone.


Extracellular changes of inorganic phosphate are different during spreading depression and global cerebral ischemia of rats.

Tissue levels of inorganic phosphate (iP-) and lactate (lac) increase during cerebral ischemia and cortical spreading depression (SD). Since cell membranes become leaky during these insults, iP- and lac were expected to leak into the extracellular space (ECS). In order to find out whether this occurs or does not, a microdialysis (MD) fiber was implanted into the cortex of anesthetized rats and extracellular lactate (lac(e)) and extracellular iP- (iPe-) were determined during various insults. Extracellular lactate increased to about the same extent during ischemia and SD. In contrast, iPe- increased during ischemia but not during SD. Instead, iPe- started to rise after SD and reached its maximum about 45 min later. The distinct pattern of iPe- in comparison to lac(e) during the above mentioned insults points to a qualitative difference of the underlying mechanisms: whereas lac appears within the ECS at any stressful situation, elevation of iP- within the ECS indicates depletion of energy stores in parallel to the lack of control of ion homeostasis.


Dimensional analysis of the human EEG and intelligence.

The purpose of this study was the determination of the relationship between the dimensional complexity of the electroencephalogam (EEG) and the level of intelligence in humans. In two experiments 34 male subjects were divided into two groups, with high and low levels of intelligence (as measured by the intelligence quotient (IQ)). During a resting phase and various mental imagery conditions the EEG was recorded from several scalp sites. Nonlinear analysis, based on the theory of deterministic chaos, revealed that subjects with high IQs demonstrate higher dimensional complexity of the EEG attractors than subjects with low IQs only during resting conditions. During performance of the imagery tasks the less intelligent subjects increase the complexity of electrical brain dynamics such that IQ-dependency vanishes. The gross (mass) neuronal manifestation of general intelligence seems to depend on task conditions and may be related to the individual brain dynamics only when no specific task is present.


Hippocampal nerve growth factor receptor immunoreactivity in patients with Alzheimer's and Parkinson's disease.

Using the monoclonal antibody, ME 20.4, against the p75 nerve growth factor (NGF) receptor, NGF receptor-like immunoreactivity has been identified in axonal processes innervating the human hippocampus, where previously a loss of reactivity has been reported in a preliminary study of Alzheimer's disease [10]. In an extended analysis of 15 cases of Alzheimer's disease, the number of NGF receptor positive fibres in the fimbria and alveus was generally decreased compared with age-matched normal groups, in presenile but not senile cases (differentiated by age of onset before or after 65 years). By contrast, in 5 demented Parkinson's disease cases (aged 61-86 years at death) immunohistochemically reactive fibres were consistently minimal or absent. This pattern of NGF receptor loss in the hippocampus most closely reflects the loss of basal forebrain cholinergic neurones, previously reported within the different clinical groups but not by biochemical measures of cholinergic function. It is concluded that even at moderately advanced stages of Alzheimer's disease with onset in the senium, axonal processes and NGF receptor mechanisms may be structurally intact in areas of cholinergic innervation from the basal forebrain, despite evidence of cholinergic dysfunction (decreased choline acetyltransferase (ChAT) and acetylcholinesterase), but that in presenile Alzheimer's and in demented Parkinson's disease cases the receptor declines in conjunction with the loss of subcortical neurones and their processes. The loss of ChAT activity may therefore reflect a dysfunction of the NGF system, in its normal maintenance of the cholinergic phenotype in basal forebrain neurones.


N-methyl-D-aspartate (NMDA)-mediated muscle relaxant action of memantine in rats.

The present study examined in vivo whether memantine exerts muscle relaxant activity via an antagonistic action at N-methyl-D-aspartate (NMDA) receptors. Intraperitoneal (i.p.) administration of memantine, 50-100 mumol/kg, reduced the tonic activity in the electromyogram recorded from the gastrocnemius muscle of spastic mutant rats. This effect was prevented by coadministration of NMDA. Memantine, while not affecting monosynaptic Hoffmann (H)-reflexes, depressed polysynaptic flexor reflexes in anaesthetized rats following i.p. (6.25-100 mumol/kg) or intrathecal (i.t., 10-500 nmol) administration. The latter effect was prevented by i.t. coadministration of NMDA, but not of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). These observations suggest that NMDA receptors might be involved in the mediation of the muscle relaxant activity of memantine.


Interleukin-6 and leukemia inhibitory factor promote the survival of acetylcholinesterase-positive neurons in culture from embryonic rat spinal cord.

Interleukin-6 (IL-6) and leukemia inhibitory factor (LIF) promoted the survival of acetylcholinesterase (AChE)-positive neurons in culture from embryonic E15 rat spinal cord. Half of the AChE-positive neurons died during 3-7 days in culture in the absence of IL-6 and LIF. However, IL-6 at a concentration of 5 ng/ml completely prevented the death of AChE-positive neurons. LIF at a concentration of 5 U/ml also stimulated the survival of neurons, although to a lesser extent than IL-6. IL-6 and LIF also increased the numbers of process-bearing neuron-like cells in culture. The dose-dependencies of IL-6 and LIF with regard to the survival of total neuron-like cells were different from those for AChE-positive neurons.


Monensin can transport calcium across cell membranes in a sodium independent fashion in the crayfish Procambarus clarkii.

Monensin, a Na(+)-selective ionophore, enhances transmitter release when applied to crustacean and frog neuromuscular junctions. Monensin is believed to raise intracellular sodium ([Na+]i) which in turn elevates intracellular calcium ([Ca2+]i). Using the fluorescent indicator fura-2, we measured [Ca2+]i in crayfish Procambarus clarkii presynaptic terminals during monensin application in normal Ringer, zero-calcium Ringer and zero-sodium Ringer to determine if [Ca2+]i increases with monensin application and if so by what mechanism. In normal Ringer, monensin, 10 microM and 100 microM, elevated [Ca2+]i by 440 nM and 7 microM respectively. This rise in [Ca2+]i was dependent on external calcium, as [Ca2+]i did not increase in zero-calcium Ringer. However, in a zero-sodium Ringer, monensin (10 microM) elevated [Ca2+]i by 370 nM. It is important to recognize that monensin, thought to be a sodium-selective ionophore, can transport calcium across the cytoplasmic membrane in a sodium-independent manner.


A postsynaptic GABA transporter in rat spinal motor neurones.

The plasma membrane uptake system for gamma-amino butyric acid (GABA) is conventionally assumed to be presynaptic, so that after release GABA could be taken up and incorporated into synaptic vesicles for re-use. Using in situ hybridization histochemistry we find that rat spinal motor neurones express GAT-1, a transporter protein for GABA, but that they do not express glutamic acid decarboxylase, the synthetic enzyme for GABA. We conclude that the uptake system is located postsynaptically in these cells. Our observation may explain previous reports where GABA has been detected immunocytochemically in motor neurones.


A novel inositol phosphate selectively inhibits vasoconstriction evoked by the sympathetic co-transmitters neuropeptide Y (NPY) and adenosine triphosphate (ATP).

Postganglionic sympathetic nerves release norepinephrine (NE) as their primary neurotransmitter at vascular and other targets. However, much evidence supports involvement of additional messengers, co-transmitters, which are co-released with NE upon sympathetic nerve stimulation and thereby contribute to their actions, e.g., vasoconstriction. Two such putative co-transmitters, neuropeptide Y (NPY) and adenosine triphosphate (ATP) have been of particular interest since they fulfill several neurotransmitter criteria. Importantly, hitherto it has been difficult to antagonize vasoconstriction evoked by either NPY or ATP with agents that are devoid of intrinsic activity. The present study describes the ability of a novel inositol phosphate, D-myo-inositol 1,2,6-trisphosphate (Ins[1,2,6]P3; PP-56) to in vitro potently block vasoconstrictor responses elicited by NPY and ATP, but not by NE, as studied in guinea-pig isolated basilar artery. The action of Ins[1,2,6]P3 does not seem to occur through antagonism at NPY- or ATP-receptor recognition sites, labeled by 125I-peptide YY and 35S-gamma-ATP, respectively, in membranes of rat cultured vena cava vascular smooth muscle cells. However, it does involve inhibition of the influx of Ca2+ induced by either co-transmitter in these same vena cava cells. It is proposed that Ins[1,2,6]P3 may be a useful functional antagonist of non-adrenergic component(s) of the vasoconstrictor response to sympathetic nerve stimulation.


Oxiracetam prevents the hippocampal cholinergic hypofunction induced by the NMDA receptor blocker AP7.

The intracerebroventricular injection of the N-methyl-D-aspartate (NMDA) receptor antagonist D,L-2-amino-7-phosphonoheptanoic acid (AP7) induces an increase of the hippocampal levels of acetylcholine (ACh) which is dose-dependent in the range 1.5-10 micrograms. Similar doses of AP7 failed to affect the ACh content of the striatum. The effect of the i.c.v. administration of 3.5 micrograms AP7 on hippocampal ACh levels was prevented by pretreatment with oxiracetam 100 mg/kg i.p. In the passive avoidance test the i.c.v. administration of 3.5 micrograms of AP7 caused severe amnesia which was antagonized in a dose-dependent manner by the pretreatment with oxiracetam. These results show that oxiracetam prevents the imbalance of cholinergic activity and the amnesia caused by blockade of NMDA receptors. The present study suggests that the hippocampal cholinergic activity is modulated by glutamatergic neuronal pathways and that the functional integrity of both systems is essential for learning and memory processes.


Uneven distribution of intracellular Cl- in rat hippocampal neurons.

Electrophysiological observations of neurons suggest that perikarya and dendrites differ in local intracellular Cl- concentration ([Cl-]i), that has not been demonstrated yet. Regional [Cl-]i in cultured hippocampal neurons was estimated using a Cl(-)-sensitive fluorescent dye. Calibration showed that perikaryonic [Cl-]i was lower than dendritic [Cl-]i. Ethacrynic acid, an inhibitor of the outwardly directed Cl(-)-pump, increased the perikaryonic but not dendritic [Cl-]i. A decrease in [Cl-]i induced by furosemide or bumetanide, inhibitors of Na+/K+/2Cl- cotransporters, was more prominent in dendrites than in perikarya. These findings suggest that uneven distribution of Cl- is generated by the region-specific localization of these transporters.


In vitro quantitative autoradiography of [125I]alpha-bungarotoxin binding at the motor end-plates of experimental autoimmune myasthenia gravis.

A quantitative evaluation was made of nicotinic acetylcholine receptors (AChR) at the motor end-plates in experimental autoimmune myasthenia gravis (EAMG). Female Lewis rats were immunized with AChR protein purified from electric organs of Narke japonica. The forelimb digit extensor muscle obtained in the chronic stage of the controls and EAMG were studied using [125I]alpha-bungarotoxin, in vitro and autoradiographically. The maximum binding capacity (Bmax) values of the controls and EAMG were calculated to be 237.7 +/- 13.0 fmol/mg (n = 4) and 42.0 +/- 4.1 fmol/mg (n = 4), respectively (P less than 0.001), and the dissociation constant (Kd) values were 11.7 +/- 1.6 nM and 7.6 +/- 0.9 nM, respectively. This in vitro autoradiographic method revealed a quantitative reduction of AChR at the motor end-plates in EAMG.


Differential subcellular distribution of PC1, PC2 and furin in bovine adrenal medulla and secretion of PC1 and PC2 from this tissue.

The subcellular distribution of PC1, PC2 and furin was determined in bovine adrenal medulla by immunoblotting of fractions obtained by density gradient centrifugation. PC1 and PC2 were found to be confined to chromaffin granules whereas furin (C-terminal-peptide) was absent from these organelles. Stimulation of bovine adrenal medulla by carbamoylcholine chloride induced the secretion of PC1 and PC2. The secreted enzymes had the same molecular size as PC1 and PC2 present in chromaffin granules.


Responses of regional cerebral blood flow to intravenous administration of thyrotropin releasing hormone in aged rats.

The effects of i.v. administration of thyrotropin releasing hormone (TRH) on regional cerebral blood flow (rCBF) were examined in both healthy adult (3-5 months old) and healthy aged (24-25 months old) male Wistar rats under halothane anesthesia. The rCBFs in 9 different brain regions-cerebral cortex, caudate putamen, hippocampus, thalamus + hypothalamus, superior colliculus, inferior colliculus, cerebellum, pons, and medulla-were measured by [14C]iodoantipyrine method. In the adult rats, i.v. administration of TRH (300 micrograms/kg) produced significant increases in rCBFs in cerebral cortex, caudate putamen, hippocampus, thalamus + hypothalamus and superior colliculus. In the aged rats, the rCBFs in all brain regions measured did not change significantly by TRH administration. From these results, it is suggested that the system involved in TRH-induced vasodilatation of cerebral blood vessels was impaired with aging.


Convergence of excitatory inputs from the chorda tympani, glossopharyngeal, and vagus nerves onto inferior salivatory nucleus neurons in the cat.

Inferior salivatory nucleus (ISN) neurons were identified by their antidromic spike responses to tympanic nerve stimulation, and their responses to stimulation of the ipsilateral chorda tympani, glossopharyngeal, and vagus nerves were investigated in urethane-chloralose-anesthetized cats. Of the 53 ISN neurons identified, stimulation of at least one of these nerves evoked spike responses in 35 (66%), and 25 (47%) were excited by inputs from more than two stimulated nerves. The mean latencies of the reflex responses evoked by stimulation of the chorda tympani, glossopharyngeal, and vagus nerves were 10.4, 13.7, and 18.9 ms, respectively.


Long-term serotonin reinnervation of the suprachiasmatic nucleus after 5,7-dihydroxytryptamine axotomy in the adult rat.

We present here immunohistochemical evidence that serotonin (5-HT) reinnervation in the suprachiasmatic nucleus (SCN) of adult rats, after intraventricular administration of 5,7-dihydroxytryptamine, is more extensive than formerly believed. The first fibers appeared at 4 months and developed until more than 7 months. However, comparison with age-matched controls showed that, even 24 months post-lesion, the density of 5-HT innervation remained abnormally low. At the electron microscopic level, many synaptic contacts were found to have been re-established. The cellular mechanisms possibly responsible for incomplete 5-HT reinnervation in the SCN are discussed.


Modulation of neonatal rat hypoglossal motoneuron excitability by serotonin.

The effects of 5-HT on neonatal rat hypoglossal motoneurons (HMs) were studied in two in vitro slice preparations. Serotonin caused either reversible depolarization or the generation of an inward current (I5-HT) in every cell tested. I5-HT persisted after synaptic blockade. In most of the cells tested, the magnitude of I5-HT was independent of membrane potential (-50 to -120 mV), and 5-HT had little effect on input resistance or slope conductance. In addition, 5-HT significantly reduced the amplitude of the post-spike medium-duration afterhyperpolarization. This reduction probably contributed to the resulting increase in the slope of the relationship describing the steady-state firing frequency response to injected current (f-I) observed in the presence of 5-HT. Thus, 5-HT increases the excitability of neonatal HMs via at least two different postsynaptic mechanisms.


Stimulation of the nucleus basalis of Meynert increases cortical cerebral blood flow without influencing diameter of the pial artery in rats.

The effects of focal electrical stimulation of the nucleus basalis of Meynert (NBM) and hypercapnia on diameter of the pial artery and regional cerebral blood flow (CBF) in the parietal cortex were examined in urethane-anesthetized rats. The diameter of pial artery was measured using the video microscope and cortical CBF was measured using the laser Doppler flowmetry. Hypercapnia at 10% of end-tidal CO2 concentration caused significant increases in diameter of the pial artery and cortical CBF. Electrical stimulation of the NBM (with parameters of 200 microA, 50 Hz, 0.5 ms, for 1 min) produced a significant increase in cortical CBF, but did not influence the diameter of pial artery. The results suggest that cholinergic fibers originating in the NBM do not contribute to neural vasodilatation of the pial artery, although they induce neural vasodilation of parenchymal blood vessels which results in an increase in CBF in the parietal cortex.


Hypoglycemia-activated K+ channels in hippocampal neurons.

Channels linking the electrical and metabolic activities of cells (KATP channels) have been described in various tissues, including some brain areas (hypothalamus, cerebral cortex and substantia nigra). Here we report the existence in hippocampal neurons of K+ permeant channels whose activity is regulated by extracellular glucose. They are open at the cell resting potential and respond to transient hypoglycemia with a reversible increase in activity. The one type so far characterized has a conductance of approximately 100 pS in isotonic K+, is inhibited by the sulphonylurea glibenclamide (1 microM), and is activated by the potassium channel opener lemakalim (0.1-1 microM). These data provide a direct demonstration of the presence, in hippocampal neurons, of glucose-sensitive channels that could belong to the KATP family.


Volume regulation of single astroglial cells in primary culture.

Relative volume variations in cultured astrocytes were examined by microspectrofluorimetry after loading the cells with the highly fluorescent intracellular probes 2,7-bis(carboxyethyl)-5,6-carboxyfluorescein (BCECF/AM) or fura-2/AM. At their isosbestic points, 450 nm and 358 nm, respectively, the probes were ion-insensitive and the fluorescent signals emitted related only to the intracellular dye concentration. By varying the excitation wavelengths, changes in intracellular pH or Ca2+ transients could be recorded simultaneously with the relative volume variations of the individual cells. After exposure to a hypotonic buffer, type 1 astrocytes swelled within 30 s and subsequently underwent regulatory volume decrease (RVD). When exposed to a hypertonic buffer, the astrocytes shrunk and exhibited regulatory volume increase (RVI). One mM glutamate induced an increase in astrocyte volume in 60 sec and evoked cytosolic Ca2+ transients but did not change intracellular pH.


Distribution of cannabinoid receptor messenger RNA in the human brain: an in situ hybridization histochemistry with oligonucleotides.

The distribution of the messenger RNA coding for the recently cloned cannabinoid receptor was studied for the first time in the human brain using in situ hybridization histochemistry and oligonucleotides probes. Microscopically, positive neurons were observed in the layers II-III and V-VI of the cerebral cortex, and in the hilus and the different dendritic layers of the dentate gyrus and Ammon's horn of the hippocampus. No additional microscopic signal could be detected. Macroscopically, a slight hybridization signal, visible on the films after 2 months exposure and which disappears after RNAse treatment, was also found throughout all layers of the cortex, in the pyramidal cell layer of the hippocampus, in the caudate and putamen, and in the granular and molecular layers of the cerebellum. No signal was detected in the brainstem, spinal cord and white matter. In conclusion, the cannabinoid receptor mRNA neuronal localizations here demonstrated in the human brain confirm our previous report in the rat, taking into account that the levels of the transcripts found in the human were lower than in the rat brain.


Interconnections between the pretectum and visual thalamus in reptiles, Caiman crocodilus.

Interconnections between the visual thalamus and the pretectum were investigated in one species of reptiles, Caiman crocodilus, by injections of horseradish peroxidase into nucleus rotundus. Nucleus pretectalis was identified as a major target of rotundal efferents as well as a significant input to nucleus rotundus. The presence of a pretectal nucleus with neural connections and topographic location similar to nucleus pretectalis of Caiman has been described in lizards and pigeons. Taken together, these observations suggest that this pretectal nuclear group and its associated fiber path may be a feature common to all non-mammalian amniotes.


Quantification of D-aspartate in normal and Alzheimer brains.

Using a new procedure to hydrolyze proteins without provoking racemization of the amino acids and using enzymatic methods to determine D- and L-aspartate (Asp), we have quantified the content of protein-bound D-aspartate (both D-aspartic acid and D-asparagine) of human brain white and gray matter proteins from normal and Alzheimer subjects. The D-enantiomer is present in brain proteins at mean concentrations between 0.48 and 0.90 mumol/g of wet tissue, corresponding to concentrations 34-82 times lower than that of L-aspartate. The highest levels of D-aspartate were found in Alzheimer gray matter (0.60-0.90, mean 0.69 mumol/g of wet tissue). When expressed as the percentage of total (i.e. D- plus L-) aspartate, %D = [D/(D + L)] x 100, the Alzheimer brains show a significantly higher content of D-aspartate in both gray matter (2.08%) and white matter (1.80%) than in the corresponding tissues of normal brains (1.65% in gray, 1.58% in white).


Mating behavior induces selective expression of Fos protein within the chemosensory pathways of the male Syrian hamster brain.

The effect of mating behavior on the expression of Fos protein was analyzed within the chemosensory pathways of the male Syrian hamster brain. Following a single mating test, the number of Fos-immunoreactive (Fos-ir) neurons increased within the amygdala, bed nucleus of the stria terminalis and medial preoptic area. The mating-induced pattern of Fos expression within these brain regions shows a strong correlation with the sites of lesions that eliminate or alter mating behavior. In addition, Fos expression was increased within the paraventricular nucleus of the hypothalamus. These results provide the first demonstration of a dynamic and selective pattern of neuronal activity within specific nuclei known to be essential for mating behavior in the male Syrian hamster.


Quantification of plaque types in sulci and gyri of the medial frontal lobe in patients with Alzheimer's disease.

beta-Amyloid protein (beta A4) deposition was characterised in the sulci and gyri of frontal cortex in 14 cases of Alzheimer's disease. A quantitative study was made of two distinct plaque sub-types (diffuse and classic) using immunocytochemistry and image analysis using a discriminant function design. As reported previously more beta A4 was observed in sulci than gyri. Diffuse plaques were more numerous than classic plaques in sulci and gyri (P less than 0.01). Classic plaques were more abundant in the sulci (P less than 0.01). Increased beta A4 deposition in the sulci is accounted for by increased numbers of classic plaques. No correlation was observed between the numbers of diffuse and classic plaques in either region. Our data suggest that the two plaque types form discrete populations and that their evolution is governed by distinct pathophysiological parameters.


Expression of neurofibromin, the neurofibromatosis 1 gene product: studies in human neuroblastoma cells and rat brain.

Neurofibromatosis type 1 (NF1) is one of the most frequent Mendelian disorders in man and one of the most common autosomal dominant disorders affecting the nervous system. The NF1 gene has recently been cloned, and shows homology to the GTPase activating protein. In order to characterize the NF1 gene product, now called neurofibromin, we raised polyclonal antibodies against C- and N-terminal regions of neurofibromin and analyzed the protein by Western blot analysis and immunohistochemical studies of rat brain.


Thalamocortical connections of rat posterior parietal cortex.

The neuronal connections of rat posterior parietal cortex (PPC) have been examined using retrograde fluorescent axonal tracers. We have found that PPC receives thalamic input predominantly from the lateral posterior and lateral dorsal nuclei, and not from the ventrobasal nucleus, which projects to the rostrally adjacent hindlimb cortex, or from the dorsal lateral geniculate nucleus, which projects to the caudally adjacent visual association area. PPC has reciprocal corticocortical connections with medial agranular cortex and orbital cortex; together, these three cortical areas may function as a network for directed attention in rats.


Spinal locomotor activity in acutely spinalized cats induced by intrathecal application of noradrenaline.

In this study we present a method of intrathecal drug administration in the acute spinal cat. A thin tube introduced into the subarachnoid space below the spinal cord was used for local drug administration. Noradrenaline reduced short-latency and provoked long-latency reflexes following high threshold afferent stimulation. Topical application of noradrenaline to the spinal cord was also able to induce and maintain locomotion. Our results strengthen the notion that noradrenergic systems play an important role in motor control. In addition, the present report introduces a protocol in the acute spinal cat, which combine the benefits associated with direct application of drugs as used in vitro experiments with the advantages of using the well investigated in vivo cat spinal cord preparation.


Effect of furosemide treatment on the central and peripheral pressor responses to cholinergic and adrenergic agonists, angiotensin II, hypertonic solution and vasopressin.

The present study was performed to investigate the effect of treatment with furosemide on the pressor response induced by intracerebroventricular (i.c.v.) injections of cholinergic (carbachol) and adrenergic (norepinephrine) agonists, angiotensin II (ANGII) and hypertonic saline (HS, 2 M NaCl). The changes induced by furosemide treatment on the pressor response to intravenous (i.v.) norepinephrine, ANGII and arginine vasopressin (AVP) were also studied. Rats with a stainless-steel cannula implanted into the lateral ventricle (LV) were used. Two injections of furosemide (30 mg/kg b.wt. each) were performed 12 and 1 h before the experiments. Treatment with furosemide reduced the pressor response induced by carbachol, norepinephrine and ANGII i.c.v., but no change was observed in the pressor response to i.c.v. 2 M NaCl. The pressor response to i.v. ANGII and norepinephrine, but not AVP, was also reduced after treatment with furosemide. These results show that the treatment with furosemide impairs the pressor responses induced by central or peripheral administration of adrenergic agonist or ANGII, as well as those induced by central cholinergic activation. The results suggest that the treatment with furosemide impairs central and peripheral pressor responses mediated by sympathetic activation and ANGII, but not those produced by AVP.


Enriched environment primes forebrain choline acetyltransferase activity to respond to learning experience.

Weanling rats were raised in an enriched or an impoverished environment. The enriched rats subsequently learned the Morris water maze faster than their impoverished counterparts. The enriched rats, both maze-trained and untrained, showed higher choline acetyltransferase (ChAT) activity in the caudate than did the impoverished, untrained rats. Maze training increased caudate ChAT in impoverished rats. Enriched but not impoverished rats showed increased hippocampal and anterior cortical ChAT activity after maze training. Thus, enrichment causes a long-lasting increase in caudate acetylcholine (Ach) synthesis and it also primes cortex and hippocampus to respond to a training experience with increased Ach synthesis.


Unilateral EEG activation during sleep in the Cape fur seal, Arctocephalus pusillus.

Sleep and wakefulness on the land were studied electrophysiologically in one adult female Cape fur seal (Arctocephalus pusillus). In two 24-h sessions, slow-wave sleep and paradoxical sleep averaged 27.4% and 4.6% of the total recording time. Almost 40% of the total slow-wave sleep time was accounted for episodes with well-defined interhemispheric ECoG asymmetry.


Eyeblinks evoke potentials in the occipital brain region.

The subjects performed voluntary eyeblinks under illuminated and dark laboratory conditions. 32-channel EEG recordings were averaged in relation to the eyeblinks and a brain electric source analysis (BESA) was performed. Two dipoles located near the eyeballs and a third dipole in the occipital region of the brain were found to explain the scalp potentials. The frontally located potentials described electromechanical potentials associated with lid movements and simultaneous eye movements. The occipitally located dipole explained a visually evoked potential with a first peak at about 180 ms after the maximum of the frontal blink potential. The visually evoked potential was observed only under illumination and was probably caused by changes in luminance during the eyeblinks.


Glial fibrillary tangles with straight tubules in the brains of patients with progressive supranuclear palsy.

A recent report has described the appearance of silver positive, tau-immunoreactive astrocytes in the brains of patients with progressive supranuclear palsy (PSP) (Neurosci. Lett., 135 (1992) 99-102). In this study we confirmed this finding in two cases of PSP by using Bodian silver staining and immunohistochemistry with antibody to human tau protein. By electron microscopy we demonstrated that fibrillary masses present in these unique astrocytes were made up of straight tubules that were indistinguishable from those of neurofibrillary tangles of PSP. The term 'glial fibrillary tangle' was proposed for these structures.


Protease 'Clipsin' extract activity reflects demographic characteristics of human brain.

'Clipsin' and other peptide bond hydrolase activities that appear to be integral membrane proteins, including two implicated in the formation of the histological hallmarks of Alzheimer's disease, were assayed in the frontal and parietal cortex from a large (n = 45) series of postmortem human brains. Tissues were extracted sequentially with detergent-containing and low ionic strength buffers. The final extracts obtained with detergent-high ionic strength buffer were assayed for peptide-bond hydrolase activity using radiolabelled casein and four chromophore-linked peptide substrates. Hydrolysis of N-succinyl-Ala-Ala-Pro-Phe-p-nitroanilide and alpha-casein showed evidence of sensitivity to the presence of Alzheimer's disease (n = 22) and some of the seven other demographic features (postmortem delay; mode of death in the case of one substrate) of the brain samples considered. By contrast, activity towards carbobenzoxy(Z)-Leu-Leu-Glu-2-naphthylamide, Z-Val-Lys-Met-4-methyl-coumaryl-7-amide and Z-Val-Lys-Lys-Arg-4-methoxy-2-naphthylamide were independent of all factors. The results are discussed in terms of damage to a sub-population of protease-containing membranes.


Oestrogen infusions into the amygdala potentiate excitatory transmission from the accessory olfactory bulb to tuberoinfundibular arcuate neurones in the mouse.

We have previously shown that oestrogen increases the percentage of tuberoinfundibular (TI) arcuate neurones that respond to electrical stimulation of the accessory olfactory bulb (AOB). This study focuses on the amygdala as a possible site for the hormonal modulation of AOB input to TI arcuate neurones. Local infusions of 17 beta-oestradiol (30 pmol) into the amygdala of ovariectomized female mice significantly potentiated excitatory responses of TI arcuate neurones to AOB stimulation. This effect appeared rapidly (less than 10 min) after infusion. The inactive oestrogen isomer, 17 alpha-oestradiol, infused in the same manner, was without effect. These results suggest that oestrogen acts directly on amygdala neurones, thereby modulating olfactory information relayed along the vomeronasal pathway to TI arcuate neurones.


Two populations of cells that express preprocholecystokinin mRNA in ventral periaqueductal grey.

Cells expressing preprocholecystokinin (CCK) mRNA in the rat midbrain periaqueductal grey area and Edinger-Westphal nucleus were analysed using in situ hybridization combined with liquid emulsion techniques. Semi-quantitative image analysis revealed that there were two populations of cells which expressed CCK mRNA. The first group of cells were large and heavily labelled and were confined to the Edinger-Westphal nucleus. The second group of cells were small and lightly labelled and were found scattered throughout ventral parts of the anterior periaqueductal grey.