TNF-receptor-1 adaptor protein FAN mediates TNF-induced B16 melanoma motility and invasion.

BACKGROUND: Locomotion of cancer cells can be induced by TNF and other motogenic factors secreted by cells of the tumour microenvironment such as macrophages. Based on our recent findings that the TNF receptor adaptor protein FAN mediates TNF-induced actin reorganisation and regulates the directed migration of immune cells responding to chemotactic cues, we addressed the role of FAN in cancer cell motility and the formation of invadopodia, a crucial feature in tumour invasion. METHODS: In B16 mouse melanoma cells, FAN was downregulated and the impact on FAN on cell motility and invasion was determined using in vitro assays and in vivo animal models. RESULTS: Like FAN(-/-) murine embryonic fibroblasts, FAN-deficient B16 melanoma cells showed defective motility responses to TNF in vitro. In vivo FAN-deficient B16 melanoma cells produced significantly less disseminated tumours after i.v. injection into mice. Danio rerio used as a second in vivo model also revealed impaired spreading of FAN-deficient B16 melanoma cells. Furthermore, FAN mediated TNF-induced paxillin phosphorylation, metalloproteinase activation and increased extracellular matrix degradation, the hallmarks of functionally active invadopodia. CONCLUSION: The results of our study suggest that FAN through promoting melanoma cellular motility and tumour invasiveness is critical for the tumour-promoting action of TNF.

Laparoscopic treatment of perforated duodenal ulcer -- a multicenter study.

AIM: The aim of this study is to evaluate the results of the laparoscopic treatment of perforated duodenal ulcer performed in 6 Romanian surgical centres with experience in the field of laparoscopic surgery. MATERIAL AND METHOD: Between 1996 and 2005, 186 patients with perforated duodenal ulcer were operated on in the centers participating in this retrospective study, all patients being ASA I-II. Thirty-nine patients (20.0%) presented mild peritonitis, 120 (64.5%) medium peritonitis and 27 (15.5%) severe (20.0%) simple suture was performed, in 110 (59.1%) suture with epiplonoplasty, for 1 (0.5%) only epiplonoplasty and 1 (0.5%) underwent excision of the perforation and suture. RESULTS: The operative time was between 30-120 minutes, with an average of 75 minutes. No death was noted. Average hospitalization time was 6 days, with periods varying between 3 and 18 days. Postoperative complications included: 5 patients (2,6%) presented infections of the abdominal walls, 1 patient (0.5%) duodenal fistula, 1 patient (0.5%) intra-abdominal abscess, 1 patient (0.5%) a superior digestive hemorrhage by "mirrored ulcer" and 1 patient (0.5%) duodenal stenosis 6 months after operation. The patients were administered 50% less analgesics, used 70% less dressings, 30% less antibiotics and had 60% less complications in comparison with those operated by the classical approach. CONCLUSION: The laparoscopic approach of perforated duodenal ulcer constitutes the first choice for patients without important co-morbidities, allowing a quick recovery and a significant reduction in the consumption of analgesics, antibiotics and dressing materials.

[Small bowel tumours from barium meal to capsule endoscopy and from open to laparoscopic approach]. / Tumorile intestinului subtire de la tranzitul baritat la enteroscopie, de la abordul clasic la cel laparoscopic.

INTRODUCTION: Tumors of the small bowel are rare and present with nonspecific symptoms. That causes a significant delay in diagnosis and consequently a worse outcome for the patient. METHODS: In a retro-prospective study we evaluated a series of 63 patients with small bowel tumors operated in the First Surgical Clinic Iasi, during 1992-2010: 18 duodenal tumors, 26 jejunum tumors and 19 ileum tumors. There were 18 (28.6%) cases with benign tumors and 45 (71.4%) cases with malignant tumors (41 primary tumors and 4 secondary tumors). We discuss problems related to diagnosis, treatment and prognosis of these tumors in the presence of new explorations (capsule endoscopy, enteroscopy) and minimally invasive approach. RESULTS: Duodenal tumors were malignant in 14 cases (11 adenocarcinomas, 3 malignant GIST tumors) and benign in 4 cases (adenoma, lipoma, GIST tumor, schwannoma) which led to stenosis in 5 cases, upper gastrointestinal bleeding in 3 cases. Positive diagnostic was confirmed with barium meal and endoscopy. The jejunal and ileal tumors were mostly malignant 31 cases (13 carcinomas, 10 lymphomas, 2 malignant GIST and one sarcoma) with only 14 cases of benign tumors (5 GIST). Their tendency was to present as emergencies: 17 obstructions and 5 peritonitis. Modem imagistic proved useful as diagnostic tool: capsule endoscopy, CT-scan and enteroscopy. The benign tumors benefited from local resection (5 cases) and segmental enterectomy (12 cases), while malignant tumors were managed using Whiple's procedures (10 cases), duodenal-jejunal resections (1 case), segmental enterectomy (29 cases), ileocolectomy (2 cases) and three bypasses. Laparoscopic approach was performed in 8 cases. CONCLUSIONS: The incidence of small bowel tumors remains low. For diagnosis, CT-scan, enteroscopy and capsule endoscopy are very useful; unfortunately the last method is not practicable in emergency. Surgery is the best choice plus chemotherapy for some malignant tumors. Laparoscopic approach is feasible in selected cases.

Substance MCS-18 isolated from Helleborus purpurascens is a potent antagonist of the capsaicin receptor, TRPV1, in rat cultured sensory neurons.

Extracts of Helleborus roots were traditionally used in the Balkan area for their analgesic action. We report that the pure natural product MCS-18 isolated from this source is a potent, specific and reversible antagonist of the capsaicin receptor, TRPV1, expressed in rat dorsal root ganglion (DRG) neurons. TRPV1 is a non-selective cation channel expressed in a subset of cutaneous and visceral sensory nerve endings and activated by noxious heat, acidity and fatty acid metabolites of arachidonic acid, with a decisive role in inflammatory heat hyperalgesia. MCS-18 inhibited the increase in intracellular calcium concentration evoked in DRG neurons by capsaicin (300 nM) and low pH (5.5) but not by heat (43 degrees C). The substance had no effect on the responses mediated by acid-sensing ion channels (ASICs) or the irritant receptor TRPA1. Whole-cell patch-clamp was used to confirm the inhibition of capsaicin-induced currents by MCS-18 which was dose-dependent. The mechanism of inhibition does not require an intact cell, as capsaicin-induced currents were also inhibited in the excised outside-out configuration. The antagonism of the capsaicin and proton action on native TRPV1 by MCS-18 may be of interest for pain therapy.

[Present trends in abdominal actinomycosis]. / Tendinte actuale în actinomicoza abdominala.

BACKGROUND: Actinomycosis is a chronic infectious disease caused by bacteria in the Actinomyces genus. The pathologic, clinic and imagistic polymorphism and the rare incidence of this disease make it so frequent misdiagnosed. MATERIAL AND METHOD: Single unit retrospective nonrandomized clinical study on over 40 years of experience in diagnosing and treating abdominal actinomycosis. RESULTS: First case of abdominal actinomycosis was diagnosed in our clinic in 1968. During the next 36 years, between 1968 and 2004, there were registered only 3 cases, all ileo-cecal actinomycosis. In the next 3 years interval, 5 more cases were diagnosed: 4 associated with intrauterine devices (IUDs) and 1 associated with intraperitoneal remnant calculi after laparoscopic cholecystectomy. We present these last 5 cases, the first 3 having been reported elsewhere. CONCLUSIONS: Abdominal actinomycosis is a rare disease, with variable and deceiving clinical and imagistic characters. In Romania we witness a shift in the epidemiology of this disease as a result of the introducing of the IUDs for the first time after 1990. Confronted with a female patient carrying an IUD that has an inflammatory and a pelvic tumoral syndrome of variable intensity, one should consider also the diagnosis of abdominal actinomycosis. Preoperative establishing of this diagnosis may allow, by a long antibiotic therapy, the elimination of the need for surgery or at least the decrease of its limits. A very rare cause of intraperitoneal actinomycosis is intraperitoneal gallstones remnant after laparoscopic cholecystectomy. To our knowledge, our case is the first reported in the medical literature.

[The absence of haptic perception in laparoscopic cholecystectomy--risk factor for biliary lesions]. / Absenta perceptiei haptice în colecistectomia laparoscopica--factor de risc pentru leziuni biliare.

BACKGROUND: Bile duct injuries are the main serious technical complication of laparoscopic cholecystectomy (LC). Each lesion is peculiar in its features as well as the surgeon's reaction when face it. AIM: To reveal the place of the human error according to accepted principles of cognitive psychology, beside other risk-factors involved in biliary accidents during LC. METHOD: Retrospective study on 18 patients treated for severe biliary lesions during LC in 1st Surgical Clinic of "Sf. Spiridon" Hospital, Iasi, Romania, between March 1993 and March 2008. According to Strasberg's classification the lesions were: type C (n=1; 3%), type D (n=13; 39.4%), type E1-2 (n=2; 6.1%) and type E5 (n=2; 6.1%). In the medical records we followed up the technical aspects of the procedure (section, dissection, clips) and the lesional and anatomic factors attended at the moment of LC. We also assessed the concerned surgeons experience based on the number of the LC at time of the biliary accident. RESULTS: In our experience (10046 LC) the incidence of the biliary injuries was 0.1% only. We met four lesional and/or anatomic factors (mean) on each case with biliary lesion. Only five cases (27.7%) were detected intraoperatively, but Spearman's correlation between time of detection and surgeons experience is insignificant. CONCLUSION: Our results, rounded with cognitive psychology data from literature, suggest the role of the absence of haptic perception during laparoscopic procedures, in the occurrence of some errors, even in circumstances with "perfect visibility".

The histopathologic type of the periampullary tumors. Is it important for survival?

BACKGROUND: The ampulla of Vater is a junction with four histologic epithelial types: ampullary, duodenal, pancreatic and biliary. The tumors of this region are named periampullary adenocarcinomas, but the histologic type of these malignancies seems to have an important significance for survival. AIM: Our purpose is to determine whether the histologic type of the resectable vaterian adenocarcinomas is a prognostic factor. METHODS: We reviewed the medical records of 38 patients who underwent RO-R1 pancreatoduodenectomy for periampullary adenocarcinomas between 1998 and 2007 in one single surgical center. The histopathologic reports and the microscopic samples were reevaluated independently by two senior pathologists. Using our database we assessed the overall survival based on histologic type, tumor stage, lymph nodes involvement, tumor size and the level of differentiation. RESULTS: The histologic type of the adenocarcinomas was intestinal in 23 cases (60.5%) and pancreatobiliary in 15 cases (39.5%). The median overall survival was significantly higher in patients with well differentiate intestinal-type in T1-T2 stage without nodes involvement. In a multivariable Cox regression analysis the regional lymph nodes involvement and the differentiation degree remained significant prognostic factors. CONCLUSION: The intestinal type of periampullary adenocarcinomas has a long survival, but the lymph nodes involvement and the lower degree of differentiation are associated with a high risk of death in these malignancies.

[Renovascular hypertension: symptoms and signs. Clinical study on 20 patients]. / Hipertensiunea arteriala de origine renala: simptome si manifestari. Studiu clinic pe 20 pacienti.

OBJECTIVES: symptoms in renovascular hypertension can be wrong interpreted, which leads to a late diagnostic, after discover the determination disease. MATERIALS AND METHODS: the study on the renovascular hypertension was made on 20 patients, aged between 2 and 36 years old, diagnosed with reno-ureteral malformations, pyelonephritis, reno-ureteral reflux and renal trauma as a determination disease, leads to manifestation types that guide the diagnostic: neuro-psychiatric signs, weight loss, renal signs and digestive signs. Beginning from these signs the arterial hypertension was diagnosed and the investigations determined the causes. RESULTS: Periodic postoperative evaluation at 3 months, during a period between 4 months and 7 years, individualised 4 evolutional clinical types: AHT with lumbar pain, AHT with no clinical signs, AHT with ophthalmologic signs and AHT with encephalitis like signs. CONCLUSIONS: symptoms in renovascular hypertension don't have pathognomonic clues and the identified signs, one type or all together, enforce the evaluation or even the monitoring of the arterial tension at least 30 days. If the values exceed the normal, complex investigations will be made in order to determine the specific cause of the AHT.

[Theoretical considerations and comments on the physiopathology in renovascular hypertension]. / Consideratii teoretice si comentarii privind fiziopatologia hipertensiunii arteriale de origine renovasculara.

The researches performed during the last four decades did not elucidate completely the pathogenic mechanism of the renovascular hypertension. The present knowledge considers that the origins of renovascular hypertension are the imbalance between the renal hypotensive system located in the medullar renal site (antihypertensive and hypotensive substances) and the renal hypertensive system (renin-angiotensin-aldosterone) located cortically. As an additional mechanism in producing hypertension is involved the disorder of hydro electrolytic metabolism, as a result of decreased excretory function, inducing an increase of plasmatic natrium level, of volemia and interstitial liquid.

[Abdominal wall endometriosis after gynecologic procedures: an under-appreciated diagnosis in general surgery]. / Endometrioza parietala abdominala dupa chirurgia ginecologica: un diagnostic subapreciat in chirurgia generala.

UNLABELLED: Incisional endometriosis is a clinical entity described in the gynecologic literature but it is not well recognized among general surgeons. The preoperative diagnosis is often mistaken for a suture granuloma, abscess, lipoma, cyst or incisional hernia. MATERIAL AND METHOD: This is a retrospective review of six cases of incisional endometriosis in our hospital aimed at determining which, if any, factors would suggest the diagnosis preoperatively. All general surgery patients with a diagnosis of endometriosis in their pathology specimens from January 1990 to February 2006 were reviewed. RESULTS: All six patients had previous cesarean sections through either a Pfannenstiel (n = 4) or lower midline (n = 2) incision. Ages ranged from 28 to 43 years (mean 34.3 years). All patients presented with a palpable painful lesion located in the area of cesarean section incision. Three of the patients had a change in symptoms with their menstrual cycle. The duration of symptoms ranged between 2 months to 6 years. All patients underwent surgical excision. The size of the excised endometrioma ranged from 3 cm to 9 cm (mean 5.3 cm). CONCLUSION: Incisional endometriosis seems to be common in women with a history of cesarean section. Most patients presented with a painful abdominal mass. Three patients presented cyclic changes in pain and size of the mass with menses, but this may be due to physician's lack of awareness and questioning. The management of choice is to remove the lesion completely even if fascial excision is required.

Grating-coupling of surface plasmons onto metallic tips: a nanoconfined light source.

We describe and demonstrate a new nanometer-scale broadband light source. It is based on the grating-coupled excitation of surface plasmon polaritons (SPPs) on the shaft of a sharp conical metal taper with a tip radius of few tens of nanometers. Far-field excitation of linear nanoslit gratings results in the resonant generation of SPPs traveling over more than 10 mum to the tip apex and converging to an intense radiative local light spot. Such nanofabricated tips are expected to find various applications in nanospectroscopy, overcoming problems with background illumination in apertureless microscopy.

[Long-term results after surgery for colorectal adenocarcinoma, stage I-III. Problems of prognosis]. / Rezultate la distanta dupa tratamentul chirurgical al adenocarcinomului colo-rectal stadiile I-III. Probleme de prognostic.

UNLABELLED: Colorectal cancer is one of the leading causes of cancer-related death worldwide. STUDY DESIGN: Prospective study on 142 consecutively cases with stage I to III colorectal adenocarcinomas (TNM AJCC/UICC) in which patients underwent potentially curative surgery in one single public health service (1st Surgical Clinic Iasi, Romania) between 2004 and 2005. MATERIAL AND METHOD: The mean follow-up was 23.26 +/- 9.78 months (range 2 to 42 months). There were 85 men (59.9%) and 57 women (40.1%) with mean age 63.38 +/- 11.84 years (range 28 to 88 years). The surgical procedures performed were the following: right colectomy (n = 54; 30%); transverse colectomy (n = 2; 1.4%); left colectomy (n = 19; 13.4%); segmental colon resection with anastomosis (n = 5 ; 3.5%); Hartmann procedure (n = 18; 12.7%); anterior rectal resection (n = 11; 7.7%) and abdominoperineal resection (n = 33; 23.2%). With regard to postoperative adjuvant therapy most patients were given chemotherapeutic agents such as 5-fluorouracil and folinic acid. The mean overall survival (months) and 42-months survival rates were calculated. The patients were censored in the survival calculation (Kaplan-Meier method) and Cox regression if they were alive at the endpoint of the follow-up. Some patients were censored because they were "lost to follow-up". Statistical significance is p < 0.05. RESULTS: The factors with a significant negative influence in overall survival and 42-months survival rates were: the age over 70 years, the emergency surgery related to cancer's complications, the advanced AJCC/ UICC stage, vascular invasion, perineural invasion, the recurrence of disease, the moderate and lower differentiated adenocarcinoma and incomplete or not performed chemotherapy. CONCLUSION: Even with a radical surgical approach the advanced stage of colorectal adenocarcinoma has a low prognostic, but some other factors have also a high significance in postoperative outcome. Related to other prognostic factors we performed a review of literature.

[Hydatic cyst of the liver. Considerations on 337 cases]. / Chistul hidatic hepatic. Consideratii asupra a 337 cazuri.

Hydatid disease of the liver is still endemic in certain parts of the world. The modern treatment of hydatid cyst of the liver varies from surgical intervention to percutaneous drainage or medical therapy. Surgery is still the treatment of choice and can be performed by the conventional or laparoscopic approach. The aim of the study is to analyze the results of the surgical treatment in hydatid disease of the liver in First Surgical Clinic, Iasi. The study concerned a period of 12.5 years (1992 - 31.07.2004) and it included 337 cases. There were performed radical procedures (ideal cystectomy - 17 cases - 5.04%, hepatic segmentectomy - 8 cases - 1.48%, atypical hepatectomy - 10 cases - 2.96%) or conservative procedures (de-roofing - 37 cases - 10.97%, subtotal pericystectomy - 34 cases -10.80%, total pericystectomy - 19 cases - 5.63%, partial pericystectomy - 212 cases -62.90%). In 35 cases (10.38%) the operation was started laparoscopically and 12 cases needed conversion. Postoperative course was complicated in 112 cases (33.32%) (external biliary fistula, cavity suppuration, residual cavity hydatid relapse). Radical methods constituted operations that had excellent results, but they are feasible in few cases. Conservative procedures, relatively simple and still accepted, have a higher rate of morbidity. The laparoscopic approach is more and more used, with good results.

[Meckel's diverticulum in laparoscopic era]. / Diverticulul Meckel în era chirurgiei laparoscopice.

A recent case of a Meckel's diverticulum diagnosed and successfully laparoscopically treated, triggered off a retrospective study on a series of 34 cases with Meckel's diverticulum admitted to the First Surgical Clinic between 1990-2003. We encountered 12 uncomplicated cases and 22 cases with a large panel of complications: 11 intestinal obstructions (volvulus 9, intussusceptions on a tumor-2), 9 cases with diverticulitis, 1 gastrointestinal bleeding and 1 case with Littre's inguinal hernia. Positive diagnosis was established intraoperatively and the surgical treatment was adapted according to the local situation (excision of the diverticulum or enterectomy). Out of 12 patients with uncomplicated Meckel's diverticulum 8 were subjected to prophylactic excision of the diverticulum. In 6 of these microscopic examinations were inclusions of gastric mucosa. Laparoscopy is safe, relatively inexpensive and efficient in the diagnosis and treatment of Meckel's diverticulum.

[Tendencies and results in rectal cancer treatment]. / Tendinte si rezultate în tratamentul actual al cancerului rectal.

UNLABELLED: Rectal cancer is one of the leading cause of cancer-related death worldwide despite of multimodal treatment. OBJECTIVE: The aim of this study is to review the management strategies for rectal cancer and to determine morbidity after multimodal therapy. METHOD: Retrospective study about 276 patients with rectal cancer surgically treated in 1st Surgical Clinic of "St. Spiridon" Hospital Iasi, Romania, between 1998-September 2003. RESULTS: There were 166 men (60.14%) and 110 women (38.86%) with mean age 63.6 years (extreme 20-81 years). The tumor's staging was: stage I--12 cases (4.5%); stage II--59 cases (21.3%); stage III--134 cases (48.2%), stage IV--71 cases (25.7%). 37 patients (13.4%) received preoperative radiotherapy (20 Gy). The tumor was resectable in 204 cases (74%) with curative purpose in 190 cases (68.8%). The postoperative therapy was performed in 198 cases (71.7%). The postoperative morbidity was documented in 32 cases and 24 patients died during hospitalisation (8.7%). Long-term results are also exposed with a review of literature. CONCLUSIONS: Rectal cancer has been notoriously difficult to treat successfully but there are numerous attempts modifying existing therapeutic regimens or designing new ones.

[Endo-Lap method in the management of biliary lithiasis (gallbladder and common bile duct)]. / Metoda Endo-Lap în tratamentul litiazei biliare (veziculare si a caii biliare principale).

AIM: To present the results of the biliary endoscopic approach (ERCP) followed by laparoscopic cholecystectomy (LC) in the management of biliary lithiasis (gallbladder and common bile duct--CBD). PATIENTS AND METHOD: From 1997 to March 2003 37 patients with biliary lithiasis were treated by endoscopic sphincterotomy (ES) with stone extraction, followed after 24-48 hours by LC. The indications for ERCP were presence of an obstructive jaundice (n=32) and a dilated CBD at the ultrasound examination (n=5). RESULTS: Selective biliary cannulation was obtained in 35 (94.6%) cases, in all of them with successful papillotomy. Stones were found in all patients. CBD clearances for calculi (from 1 to 8) was obtained in 33 of 35 patients (94.3%), the rest of 2 being managed by open laparotomy. Antibiotics were administrated in all patients. Laparoscopic cholecystectomy was performed after 24-48 hours, with one conversion (3%). Postoperative morbidity was 12.1%: 2 transitory pancreatic reactions and 2 wound infections. CONCLUSION: Endo-Lap method is a useful management alternative for combined gallbladder and CBD lithiasis. It has all the advantages of the two mini-invasive procedures (fast recovery, short hospitalization, low costs) and a less postoperative morbidity in patients with high risk.

[Congenital cystic disease of the biliary system in adults]. / Dilatatia chistica congenitala a cailor biliare la adult.

Congenital cystic disease of the biliary system is a complex syndrome of ectasies of the intra-, extra- or both situation of biliary tree. This disease has an unsure etiopathogeny. It is uncommon through the third age, with a greater incidence in child, teen-ager and young adult. The goal of our study is to evaluate the symptoms, diagnosis, treatment and histological aspects of the congenital biliary cysts. We performed a retrospective study from March 1988 to July 2003 about 11 patients with this disease treated in our surgical clinic. Clinical features, methods of diagnosis and surgical treatment were assessed. All patients were females with mean age 51 years (extreme 26-77 years). The symptoms were: right upper quadrant pain--11 cases (100%), jaundice--6 cases (54.5%), fever--3 cases (27%), palpable abdominal mass--2 cases (18%), weight loss--1 case (9%). The imaging diagnosis was helpful (ultrasonography, CT, ERCP, percutaneous cholangiography and preoperative cholangiography). In concordance with Todani classification the patients were included in the following types: Ia--3 cases (27%), I b--1 case (9%), I c--3 cases (27%), IV a--2 cases (18%), IV b--1 case (9%), V--1 case (9%). All patients were operated on: after cholecystectomy and transcystic cholangiography (11 cases--100%) we performed the total excision of the cyst--9 cases (82%) with choledochal jejunostomy (Roux-en-Y)--6 cases (54.5%), choledochal jejunostomy (omega)--1 case (9%) and choledochal duodenostomy--2 cases (18%). In one case of neoplasic cyst with portal invasion we performed a cyst-jejunostomy (omega) and in one case of Caroli disease with total obstruction of the distal choledoc, the solution of choice was choledocal-duodenostomy. The microscopic pathology of the cyst wall showed: chronic intramural inflammation--9 cases (82%) and the absence of the nervous intramural terminations--1 case (9%). The additional lesions was: hepatic cirrhosis--1 case (9%) and hepatic fibrosis--3 cases (27%). We found three cases with neoplasia: malign cyst with advanced local invasion--1 case (9%), pancreatic carcinoma--1 case (9%) and gallbladder carcinoma (microscopic finding)--1 case (9%). The postoperative morbidity includes biliary fistula--2 cases (18%) and wound infection--2 cases (18%). Long-term follow-up revealed cholangitis in one case--9%. The cystic dilatations of the common bile duct is an exclusive indication for surgery as soon as it was discovered.

[Giant retroperitoneal lipoma]. / Lipoame gigante retroperitoneale.

70 retroperitoneal tumors (10 with an adipous origin out of which 8 were lipomas) have been operated upon in our clinic since 1985. Four cases of giant lipomas are presented in this paper. They weighed 4.5-7.5 kg. and had a diameter over 15 centimeters. Their close proximity with the kidney, duodenum, colon, inferior vena cava etc made there extirpate difficult. The post-operative condition of the patients was good. Although the histopathological tests proved that all these giant lipomas were benign after two to four years, their relapse required a new surgical intervention. The histopathology of the relapsed lipomas revealed a malign degeneration in 3 out of the four cases. The origin of this malign degeneration was in the fibrous part of the tumors.

The MSH-like activity of pineal hormone E5 in vivo and in vitro experiment.

Further experiments have revealed that the polypeptidic hormone E5 has a MSK-like effect, as experimentally demonstrated on the frog skin. In Rana esculenta, 30-120 min after a subcutaneous injection of 0.2 mg purified E5B or E5P/100 g b.w., the skin blackened and the effect lasted for about two hours. A comparable effect was induced by incubating the fragment of frog abdominal skin with a similar solution of E5. This MSK-like effect appears to be identical upon mammalian melanocytes in C57/B16 mice strain valves in vitro experiment. The results obtained indicate that pineal gland can influence melanocyte activity directly and suggest the possible implication in such pathological conditions as melanomas, vitiligo, etc.

Pineal-pancreas interaction: pineal hormone E5 action on insulin activity.

We studied the E5 pineal hormone influence on glucidic metabolism, especially on insulin. Our investigations included the metabolic processes i.e. muscular glycogen biosynthesis and glycemia, as well as serum insulin uptake. Male rats and rabbits (lots of 5 animals) were injected (i.p. or i.v.) with E5B saline sol. (0.1 mg/ml) at various time intervals (30 min for model A or 60 min and 30 min for model B) before sacrifice. We observed the E5 influence on the insulin-induced biosynthesis of glycogen after 60 min (model A). The module (+/- % as control) of variations was positive for low and average concentrations of insulin. This findings emphasize an insulin-like activity or an increasing effect of the E5 hormone. For higher concentrations (above 900 mU insulin), an inhibitory effect was obtained. This action is time-dependent (150-270 min). The insulin-'enhanced' effect turns into an 'inhibitory' one after 330 min. An inhibitory effect of E5 on the simultaneous administration of both hormones was also obtained. We observed a significant increase of the high values (2.0-2.5 mg/ml) of the blood glucose (glycemia) at 270 min. The glycemia values distribution presupposes a hyperglycemic-type activity of the E5 hormone. We recorded an increase of the plasma insulin (at 30 min), followed by its decrease (at 60 min). The decrease goes on up to 240 min. The insulin values tend to rise again to the initial level up to 720 min. (model A and B). These observations suggest that E5 activity on insulin is acute (at less than 30 min) and effective for longer than 7 hours.(ABSTRACT TRUNCATED AT 250 WORDS)