Cutting efficiency of conventional and heat-treated nickel-titanium rotary or reciprocating glide path instruments.

AIM: To compare the cutting efficiency of several glide path files: HyFlex EDM Glidepath File (HEGF), One G (OG), R-Pilot (RP) and WaveOne Gold Glider (WOGG) at different cutting inclinations. METHODOLOGY: Cutting efficiency of 120 new HEGF, OG, RP and WOGG was tested at 90°, 70° and 45° inclination in relation to the sample. Depending on manufacturer instructions, instruments were tested in continuous rotation or reciprocating motion against standardized gypsum samples for 120 s using a customized apparatus. Cutting efficiency was determined by measuring the weight loss and the length of the sample cut. Data were analysed using two-way analysis of variance and Tukey t-test (P < 0.05). RESULTS: RP and WOGG had greater cutting ability than HEGF and OG in all tested angles. RP tested at 45° had significantly greater cutting efficiency than when tested at 90° and 70° (P < 0.05). OG was not significantly different in terms of cutting ability at 90°, 70° and 45° (P > 0.05). HEGF and WOGG had significantly greater cutting efficiency at 45° and 70° compared to 90° (P < 0.05), with no significant difference between 45° and 70° (P > 0.05). RP had the greatest cutting ability at all tested angles. CONCLUSIONS: Reciprocating glide path instruments had greater cutting efficiency compared to those in continuous rotation. An inclined insertion (45° or 70°) increased the cutting ability of glide path files except for One G conventional NiTi files.

Neoplastic sigmoid-uterine fistula. An exceptional complication of large intestine cancer.

Neoplastic sigmoid-uterine fistula is an extremely rare condition because the uterus is a thick and muscular organ. A 74-year-old woman was admitted to the First Aid Station suffering from abdominal pain and foul smelling vaginal discharge. Gynaecological examination showed fecal drainage from the cervical orifice, while the uterus was regular in size but very firm and painful. Ovaries and fallopian tubes were not palpable owing to abdominal tenderness. Ultrasounds reveled inhomogeneous thickening of uterine cavity, without detecting fistula. Contrast Medium CT (CMCT) showed Douglas' recto-uterine pouch occluded. The sigmoid wall was very thin exception a site where a fistula was suspected. At the surgery severe adhesions of the sigma-rectum with the posterior uterine wall were observed. After adhesiolysis, 18 cm colon-sigma-rectum was removed. Total hysterectomy with salpingooophorectomy was performed. Lymphadenectomy ended the procedure. Anatomical specimen confirmed sigmoid-uterine fistula. At histology a mildly differentiated adenocarcinoma of sigma-rectum was shown. Postoperative course was uneventful. Such a case of neoplastic sigmoiduterine fistula has not been reported so far.

Surgical removal of multiple mesenteric fibroids (Kg 4,500) by abdominal spread of previous laparoscopic uterine myomectomy.

INTRODUCTION: Huge and multiple mesenteric fibroids (4,500 Kg weight) are very unusual. In many cases they are mistaken for subserosal fibroids of the womb due to the proximity with uterine walls. When they have a rapid growth, the risk of becoming malignant (sarcoma) has not to be underestimated. Surgery is challenging to remove abdominal nodes. CASE REPORT: A case of a 40-year old woman, admitted to the hospital with abdominal masses occupying the entire cavity was reported. Both computerized tomography (CT) and ultrasounds (US) were not diriment for belonging of tumours. Clinical history of patient reports a laparoscopic removal of uterine fibroids, using the morcellator. Laparoscopy was performed four years before. Open surgery by means of a large transversal suprapubic laparotomy according to Pfannestiel was carried out. Multiple and huge mesenteric, peritoneal and intestinal tumours spread in the whole abdominal cavity were found, removed and examined by frozen section histology; in addition a series of small conglomerated myomas in the site of previous laparoscopic transumbilical route was taken away as well (the largest fibroid weighed Kg 3.500 and the all tumors removed 4,500 Kg); the result was benign (fibroids) and genital apparatus was preserved. Operation was challenging. Postoperative course was uneventful; after five days patient was discharged. CONCLUSIONS: This case is very interesting for many factors: A) many extra-uterine fibroids spread throughout abdominal cavity; B) considerable weight of the masses C) intraoperative and postoperative danger. Finally, due to involvement of previous laparoscopic transumbilical incision together with other findings, the hypothesis of post laparoscopic dissemination has to be considered. A case of so large extragenital abdominal fibroids following laparoscopic uterine myomectomy has never been published so far.

How to prevent mesh erosion in transobturator Tension-Free Incontinence Cystocoele Treatment (TICT): a comparative survey.

BACKGROUND: Tension-Free Incontinence Cystocoele Treatment (TICT) was introduced by Leanza-Gasbarro-Caschetto in 2001, on the basis of experimental and clinical investigations to obtain a physiologic mechanism of closure and opening of the urethra in the event of genuine stress urinary incontinence (S.U.I.) and cistocoele. TICT took origin from the previous retropubic tension-free vaginal tape (TVT) based on the integral theory according which mid-urethra has a main role for urinary continence but differs in that the former restores the anatomy and physiology of the entire anterior compartment. Simultaneously Delorme in 2001 spread the TOT (Trans-Obturator Tape) technique, emphasizing the needle passage across the obturator foramen which represents a new and less invasive route in comparison with the retropubic one. Trans-obturator TICT exploits the advantages of TOT, adding the anatomical repair of bladder prolapse. Introduction of mesh for treatment of pelvic defects gives a lower rate of recurrence, but introduces new complications due to the extraneous materials, among which the most common is represented by mesh erosion. At present the rate of mesh erosion reported is 4.7% in the TOT. Aim of our survey was to verify a technique allowing post-operative erosion prevention. PATIENTS AND METHODS: 230 women with urodynamic stress incontinence and cystocoele after diagnostic phase were allocated to 2 treatment groups (A end B-group), with open alternative method. Agroup women underwent transobturator TICT procedure after preparation of anterior compartment by means of a transversal incision taking care to preserve the integrity of the vaginal skin in the site where the mesh would be allocated. Conversely, B-group transobturator TICT was carried out in a classical way, through a longitudinal incision of anterior vaginal skin and suturing after placing the mesh. Each of the two groups was initially constituted by 115 subjects. There were 14 preoperative dropouts among which 6 (115-6=109) in A-group and 8 (115-8=107) in B-group and, after, 16 postoperative dropouts including 7 (109-7=102) in the former and 9 (107-9=98) in the latter. Other pelvic defects were solved during the same operation for a complete repair of pelvic floor. RESULTS: A-group: subjectively SUI was cured in 87/102 (85.3%) objectively, SUI was cured in 88/102 (86.3%) of patients; cystocoele in 87/102 (85.3%). B-group: subjectively SUI was cured in 86/98 (87.7%) and objectively in 87/98 (88.8%) of patients; cystocoele was solved in 86/98 (87.7%). Between the two groups both anti-incontinence end cystocoele treatment was superimposable (p value > 0.05). Nevertheless regarding mesh erosion, a percentage of 5.1% (5/98) was found among B-group while none among A-group patients where integrity of vaginal skin beneath the mesh was preserved. CONCLUSION: Integrity of the vagina beneath the mesh is the right.key to prevent ad externum mesh erosion.

Hydronephrosis and utero-vaginal prolapse in postmenopausal women: management and treatment.

INTRODUCTION: Pelvic organ prolapse is a multifactorial disease. Aim was to evaluate the effect of the whole surgical correction of pelvic floor on hydronephrosis due to severe prolapse. PATIENTS AND METHODS: A retrospective case study on 250 patients presenting with severe uterovaginal prolapse was carried out. RESULTS: Hydronephrosis was found in 32/234 (13.7 %). All patients underwent hysterectomy, vaginal apex axial suspension, posterior and anterior repair, vaginally. Prepubic TICT (Tension free Incontinence Cystocoele Treatment) was done in 38 cases (3 with hydronephrosis). Of the 32/234 (13.7 %) patients with hydronephrosis, 18/32 (56.25%) had complete resolution of hydronephrosis after treatment, 14/32 (43.75%) had a reduction of calico-pyelic dilatation, among them 8 patients had a second degree and 6 a first degree of hydronephrosis. CONCLUSIONS: Vaginal-hysterectomy, axial apex suspension, anterior and posterior repair resulted in either complete resolution or improvement of hydronephrosis. Prepubic TICT did not interfere on mechanical obstruction and maintained postoperative continence in the event of occult Stress Urinary Incontinence (SUI).

Colorectal cancer in aged patients. Toward the routine treatment through laparoscopic surgical approach.

AIM: Colorectal cancer is one of the most common malignancies in general population. The incidence seems to be higher in older age. Surgery remains the treatment of choice and laparoscopic approach offers numerous benefits. We report our personal experience in elderly patients operated on for colorectal cancer with laparoscopic resection. PATIENTS AND METHODS: From January 2003 to September 2013, out of 160 patients aged 65 years or older and operated with minimally invasive techniques, 30 cases affected by colorectal cancer and operated on with laparoscopic approach were analyzed in this study. RESULTS: Male/female ratio was 1.35 and mean age 72 years. Constipation, weight loss, anemia and rectal bleeding were the most commonly reported symptoms. Lesions involved descending-sigmoid colon in 53% of cases, rectum in 37% and ascending colon in 10%. Among laparoscopic colo-rectal operations laparoscopic left colectomy was the most frequently performed, followed by right colectomy, abdominoperineal resection and Hartmann procedure. Operative times ranged from 3 to 5 hours depending on surgical procedure performed. Mean hospital stay was 6 days (range 4-9). Conversion to open approach occurred only in a case of laparoscopic right colectomy (3%) for uncontrolled bleeding. A single case of mortality was reported. In two cases (7%) anastomotic leakage was observed, conservatively treated in one patient and requiring reoperation in the other one. CONCLUSIONS: Laparoscopic colorectal surgery is feasible and effective for malignancies in elderly population offering several advantages including immunologic and oncologic ones. However an experienced surgical team is essential in reducing risks and complications.

Comparison between three mini-sling surgical procedures and the traditional transobturator vaginal tape technique for female stress urinary incontinence.

OBJECTIVES: To compare mini-sling and traditional tension-free operations for female stress urinary incontinence. STUDY DESIGN: A systematic review of articles in the Literature published between 2002 and 2012, was conducted. A Pubmed search was performed. Primary outcomes were subjective and objective cure rates at 12 months comparing the three single-incision mini-slings techniques (TVT-Secur, MiniArc and Monarc systems) with the standard midurethral sling procedure TOT (Transobturator Vaginal Tape). Secondary outcomes included peri-operative (vaginal and/or bladder perforation, urine retention, urinary tract infection, bleeding, pain) and post-operative (mesh exposure, de novo urgency, and dyspareunia) complications. RESULTS: In term of objective cure rate at 12 month after surgery, it is evident that TOT at first, and MiniArc are the most effective procedures. The incidence of post-operative urgency and UTI was lower in TOT technique, while vaginal perforation was described in equal frequency both in TOT and in MiniArc procedures. The advantages of the three above described mini-invasive techniques seem to consist into lower cases of urinary retention, pain and bleeding. Furthermore, bladder perforation and bleeding are not described in the Literature for TVT-Secur and Monarc systems. CONCLUSIONS: Some single-incision slings look promising and as effective as conventional sub-urethral slings at short term evaluation. However, at this moment a clear statement in favor of the widespread use of single-incision slings cannot be made. More studies must define the efficacy of these techniques.

Surgical repair of rectocele. Comparison of transvaginal and transanal approach and personal technique.

Rectocele is defined as a herniation of the rectal wall inside the vagina due to a defect of the recto-vaginal septum. It is traditionally considered a posterior compartment damage with weakness of posterior vaginal wall support resulting in a bulging of the rectum into the vaginal cavity. One of the main causes of rectal prolapse is the operative vaginal birth, although the evidence of the defect may occur after many years The treatment of rectocele is surgical, and the approach can be transperineal, transvaginal, and transanal or, in selected cases, transperitoneal through open or laparoscopic techniques. In this study we compare two transvaginal surgical techniques - i.e. the perineal body anchorage to the posterior septum and the traditional Denonvilliers' transversal suture after removing of the vaginal skin, with the mostly performed transanal procedure, the STARR - comparing the data from the literature on their results. Mean hospital stay, rectal symptoms, dyspareunia, quality of life, recurrence rate and postoperative complications have been considered. Both transvaginal and transrectal surgical techniques are effective to solve posterior compartment defect and to improve the quality of life. Vaginal approach may interfere with the sexual activity; furthermore it is associated with minimal postoperative pain than the transanal approach. Better anatomic results are assured after endovaginal surgery, while better rectal function prevail after the transanal approach. Vaginal techniques are more suitable to gynecologists, whereas the transrectal ones are usually performed by colo-proctologists or general surgeons.

Laparoscopic removal of a giant paratubal cyst complicated by hydronephrosis.

Paratubal cysts represent approximately 10% of all adnexal masses. In most cases they are very small, but very few cases are reported in the literature where they exceed 15 cm of diameter. Furthermore, giant paratubal cysts complicated by bilateral hydronephrosis are unique. The Authors describe a case of a huge paratubal cyst (30 cm in diameter), in a 14 year old obese girl, treated by complete laparoscopic enucleation.

A didactic protocol for labour and delivery: the partogram.

AIM: The aim of this paper was to evaluate the didactic protocol on the management of both labour and birth. METHODS: Selection criteria were carried out with randomized, quasi-randomized controlled trials and other relevant articles involving a comparison of partogram with no partogram, or comparison between different partogram designs. A printed alert and/or action lines are designed to prevent the deviation. Particularly partograms where divided in: 1) partogram versus no partogram in labour-delivery; 2) partogram with two-hour action line versus partogram with four-hour action line; 3) partogram with two-hour action line versus partogram with three-hour action line; 4) partogram with three-hour action line versus partogram with four-hour action line; 5) partogram with alert line versus partogram with alert and action line; 6) earlier versus later intervention. RESULTS: We included twenty-eight studies in this review, involving 7 827 women; six studies assessed partogram versus no partogram and the remainder assessed different partogram designs. There was no evidence of significant difference between partogram and no partogram in caesarean section. When compared the use or less of partogram in vaginal deliveries, this tool with defined management protocols prevents obstructed labour (protracted phase or arrest of dilatation). Quality monitoring of the labour with the partogram will reduce the morbidity and mortality in both mother and newborn. Deviation of the curve from the standard partogram is an alert graphic expression of risk and moves forward an adequate management of treatment. Regarding the use of partogram as didactic protocol, it is considered useful in the comprehension of the various evolutions of labor and delivery. CONCLUSION: On the basis of literature, the data regarding the use of partogram is controversial. Regarding elective caesarean section partogram doesn't give any advantages owing to the absence of labor. Relating the employ of partogram in labour, it is helpful for correcting the deviation from the normality, permitting the opportune use of both drugs (oxytocin) and procedures (amniotomy). Even if the literature does not recommend a routine use of the partogram as part of standard labour management, it always represents an instrument for a better determination of the parameters evaluated (dilatation, mechanical curve, contractions). Both physicians and midwives have to be trained to a correct use the partogram in order to have satisfactory results. A challenge to improve the graph and facilitate the compilation of the model should be addressed. Further trial evidence is required to establish the real and significant utility of partogram. Besides, the partogram is a practical graph for medico-legal evaluation in case of contentiousness.

Minilaparotomic incision for haemorrhagic corpus luteum: a case report.

Corpus luteum cyst rupture with consequent hemoperitoneum is a common cause of admission to the emergency room. This condition is frequently misdiagnosed because of overlapping of clinical findings in acute gynecologic diseases. However, an incorrect identification may lead to delay in surgical treatment, which can Romabe a life-threatening condition. Ultrasound (US) is the first technique used for diagnosis that can confirm or dismiss the presence of intraperitoneal fluid. Secondly, the contrast-enhanced computed tomography (CT) is the quickest way to identify the site of active bleeding and to establish the correct management of the clinical condition. Herein, we report a case of a 19-years-old girl with acute abdominal pain correctly identified by diagnostic images and treated with mini-invasive surgery techniques in order to quickly act without clinic and aesthetic sequelae.

A rare case of trichilemmal ovarian carcinoma. Case report and review of the literature.

Trichilemmal ovarian carcinoma is very rare. A 52-years-old woman was admitted to University Hospital Department suffering from pain in the left iliaca fossa lasting for three months. Uterus was normal in size, painless as well as right adnexum. On the left site ovary was increased in volume and slightly sore. Transvaginal ultrasounds showed a 97x65x86 mm mixed vascularized unilocular mass. CT scan detected a pelvic expansion with a heterogeneous density due to the presence of different structures varying from fat to bone tissue. A proper informed consent was obtained and a suprapubic transversal laparotomy according to Pfannenstiel was carried out. Ovarian mass and ipsilateral tube were removed with no rupture. The anatomical extemporaneous result was of benign dermoid cyst. The postoperative course was uneventful and after three days the patient was discharged in regular conditions and was recommended to come for final anatomical result. Following a month, the final histological answer was of 15 mm trichilemmal malignant tumor in a context of a large benign dermoid cyst. The neoplastic lesion appears to be entirely contained within the limits of the swollen mass. The outer surface was with no lesions. A case of trichilemmal malignant tumor involving ovary has not been published so far.

CT-guided drainage with percutaneous approach as treatment of E. Faecalis post caesarean section severe abscess: case report and literature review.

We report a case of a 32-year old woman with severe pelvic abscess formation who was readmitted to the hospital after ten days of postoperative caesarean course. The patient had undergone emergency caesarean section (CS) for acute foetal sufferance during expulsive period and following three days had been discharged regularly. Enterococcus Faecalis was isolated from purulent material. A prompt antibiotic therapy was carried out, therefore clinic condition did not improve. A percutaneous Computed Tomography (CT)-guided drainage of the abscess was planned. Under local anesthesia abscess was drained. The hospitalization stay allowed monitoring the patient's clinical condition and laboratory blood panel until normalization of all parameters.

Nuck canal cyst involving right femoral vein: management and therapy of a rare clinical case.

We present a very rare case of a 49-year old woman suffering from Nuck canal cyst reaching and compressing femoral vein. Nuck canal cyst is very uncommon event because the pouch accompanying the gubernaculum during intrauterine descent of ovaries usually obliterates, whereas when it persists a cystic cavity containing citrine fluid develops. A gravid 0 para 0 49 old woman was admitted to Catania University Surgery Department owing to suspected lymphatic tumor compressing right femoral vein and causing groin pain with ipsilateral leg partial stasis. Patient believed right venous stasis was due to fibromatous uterus. Ultrasounds and computed tomography (CT) scan defined size (7.1 × 4.2 × 1.5 cm), structure (cystic) of mass and its relation with femoral vein, although they were not diriment for diagnosing its nature. Color Doppler detected circulatory function of compressed femoral vein. Surgery was challenging and Nuck cyst was removed after accurate separation from the right femoral venous walls. A case of Nuck cyst involving femoral vein has never been reported so far.

Intracesarean removal of two huge fibroids occupying the whole uterine fundus: a case report.

Uterine fibroid is an estrogen-dependent mass growing during pregnancy. Caesarean myomectomy (CM) is a controversial procedure. A 35-year-old obese (106 Kg) patient gravida 2 para1 (caesarean section), undergoing caesarean section, had two myomas occupying the whole uterine fundus (104.2 mm and 50 mm respectively). Intracesarean myomectomy was carried out after extraction foetus (Apgar score: 9/10). Postoperative course was uneventful and patient was discharged after four days.

Extensive training in a maze task reduces neurogenesis in the adult rat dentate gyrus probably as a result of stress.

It has recently been shown that hippocampal neurogenesis can be modulated either directly or indirectly by ascending cholinergic inputs from the basal forebrain. In the present work, we sought to address whether extended training in a spatial navigation task would affect hippocampal neurogenesis in the presence of a severe and selective cholinergic depletion. Young female rats received stereotaxic injections of the immunotoxin 192 IgG-saporin into the basal forebrain nuclei and/or the cerebellar cortex. Starting from 4 to 5 weeks post-lesion, and for the subsequent 2 weeks, the animals were trained on paradigms of reference and working memory in the water maze and received single daily i.p. injections of bromodeoxyuridine (BrdU) at the end of each testing session. In line with previous observations, a dramatic 80% decrease in neuron proliferation was seen in the dentate gyrus of lesioned animals, as compared to vehicle-injected or intact controls. Interestingly, however, rats subjected to maze training over 2 weeks, irrespective of their learning success, exhibited significantly fewer newborn neurons than matched controls with no maze exposure. Thus, at least for the type of task used here, which has previously been shown to impose a certain degree of stress, extended training and learning does not appear to affect proliferation in the dentate gyrus.

Extensive reinnervation of the hippocampus by embryonic basal forebrain cholinergic neurons grafted into the septum of neonatal rats with selective cholinergic lesions.

Reconstruction of the septohippocampal pathways by axons extending from embryonic cholinergic neuroblasts grafted into the neuron-depleted septum has been explored in the neonatal rat by using a novel lesioning and grafting protocol. Neonatal ablation of the basal forebrain cholinergic projection neurons, accompanied by extensive bilateral cholinergic denervation of the hippocampus and neocortex, was produced at postnatal day (PD) 4 by 192 immunoglobulin (IgG)-saporin intraventricularly. Four days later, cholinergic neuroblasts (from embryonic day 14 rats) were implanted bilaterally into the neuron-depleted septum by using a microtransplantation approach. The results show that homotopically implanted septal neurons survive and integrate well into the developing septal area, extending axons caudally along the myelinated fimbria-fornix and supracallosal pathways that are able to reach the appropriate targets in the denervated hippocampus and cingulate cortex as early as 4 weeks postgrafting. Moreover, the laminar innervation patterns established by the graft-derived axons closely resembled the normal ones and remained essentially unchanged up to at least 6 months, which was the longest postoperative time studied. The reinnervating fibers restored tissue choline acetyltransferase activity (up to 50% of normal) in the dorsal hippocampus and the parietooccipital cortex. Retrograde labeling with Fluoro-Gold from the host hippocampus combined with immunocytochemistry confirmed that most of the projecting neurons, indeed, were cholinergic. The results suggest that the graft-host interactions that are necessary for target-directed axon growth are present in the septohippocampal system during early postnatal maturation. Thus, the present approach may contribute to overcome the functional limitations inherent in the use of ectopically placed intrahippocampal transplants.

Effects of neonatal lesions of the basal forebrain cholinergic system by 192 immunoglobulin G-saporin: biochemical, behavioural and morphological characterization.

Selective removal of the basal forebrain cholinergic neurons by the immunotoxin 192 immunoglobulin G-saporin has offered a new powerful tool for the study of the relationships between cholinergic dysfunction and cognitive impairments. In the present study the morphological and functional consequences of selective lesions of the basal forebrain cholinergic system during early postnatal development have been investigated following bilateral intraventricular injections of 192 immunoglobulin G-saporin to immature (four-day-old) rats. Administration of increasing doses (0.2-0.8 microgram) of the immunotoxin produced dose-dependent loss of cholinergic neurons in the septal/diagonal band area (up to 72-86%) and in the nucleus basalis magnocellularis (up to 91-93%), paralleled by marked reductions in choline acetyltransferase activity in the hippocampus and several cortical regions (73-84%). The parvalbumin-positive neurons in the septal/diagonal band area and the calbindin-positive Purkinje cells in the cerebellum were unaffected at all dose levels. Brain dopamine or noradrenaline levels were unaffected or increased by the immunotoxin treatment. At the optimal dose, 0.4 microgram, the toxin conjugate produced maximal cholinergic depletion without significant mortality. Higher doses (0.8, 1.2 and 1.6 micrograms) of toxin, on the other hand, proved to be lethal for most or all of the injected animals. When tested at three and eight months after the optimal dose, in spite of persisting cholinergic depletion, the noenatally lesioned animals showed no impairment in the water maze task or in locomotor activity and exploration as compared to normal controls, probably reflecting partial sparing of the cholinergic neurons by the neonatal immunotoxic lesion (above all in the vertical and horizontal limbs of the diagonal band area), and/or a greater degree of plasticity in the developing as compared to the mature cholinergic system. The place navigational performance of the neonatally lesioned animals in the water maze task was abolished by central muscarinic cholinergic receptor blockade (by atropine) or by a second immunotoxic lesion, which eliminated virtually all residual cholinergic neurons in the septal/diagonal band area and the nucleus basalis. Administration of 192 immunoglobulin G-saporin to similarly trained, but previously normal adult rats, produced similar cholinergic depletions but much less severe place navigation deficits, suggesting that preoperative training on the task may reduce the functional consequences of a subsequent cholinergic lesion. The results thus support the view that the basal forebrain cholinergic system may be implicated in the acquisition rather than retention of spatial memory in the water maze task.

Septal cholinergic neurons suppress seizure development in hippocampal kindling in rats: comparison with noradrenergic neurons.

Widespread lesions of forebrain cholinergic or noradrenergic projections by intraventricular administration of 192 IgG-saporin or 6-hydroxydopamine, respectively, accelerate kindling epileptogenesis. Here we demonstrate both quantitative and qualitative differences between the two lesions in their effects on hippocampal kindling in rats. Epileptogenesis was significantly faster after noradrenergic as compared to cholinergic denervation, and when both lesions were combined, kindling development resembled that in animals with 6-hydroxydopamine lesion alone. Furthermore, whereas the 192 IgG-saporin lesion promoted the development only of the early stages of kindling, administration of 6-hydroxydopamine or both neurotoxins accelerated the late stages also. To investigate the contribution of different subparts of the basal forebrain cholinergic system to its seizure-suppressant action in hippocampal kindling, 192 IgG-saporin was injected into medial septum/vertical limb of the diagonal band of Broca or nucleus basalis magnocellularis, leading to selective hippocampal or cortical cholinergic deafferentation, respectively. The denervation of the hippocampus facilitated kindling similar to the extensive lesion caused by intraventricular 192 IgG-saporin, whereas the cortical lesion had no effect. These results indicate that although both noradrenergic and cholinergic projections to the forebrain exert powerful inhibitory effects on hippocampal kindling epileptogenesis, the action of the cholinergic system is less pronounced and occurs specifically prior to seizure generalization. In contrast, noradrenergic neurons inhibit the development of both focal and generalized seizures. The septo-hippocampal neurons are responsible for the antiepileptogenic effect of the cholinergic system in hippocampal kindling, whereas the cortical projection is not significantly involved. Conversely, we have previously shown [Ferencz I. et al. (2000) Eur. J. Neurosci., 12, 2107-2116] that seizure-suppression in amygdala kindling is exerted through the cortical and not the hippocampal cholinergic projection. This shows that, depending on the location of the primary epileptic focus, i.e. the site of stimulation, basal forebrain cholinergic neurons operate through different subsystems to counteract seizure development in kindling.

Regulation of neurotrophin and trkA, trkB and trkC tyrosine kinase receptor messenger RNA expression in kindling.

Levels of messenger RNA for nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3, and the tyrosine kinase receptors trkA, trkB and trkC have been studied using in situ hybridization in the rat brain 2 h and four weeks after kindling-induced seizures. Epileptiform activity evoked by hippocampal stimulation and exceeding 70 s lead to a concomitant and transient increase of brain- derived neurotrophic factor, nerve growth factor, trkB and trkC messenger RNA expression in dentate granule cells after both focal and generalized seizures. Brain-derived neurotrophic factor messenger RNA levels were also increased bilaterally in the CA1-CA3 regions, amygdala and the piriform, entorhinal, perirhinal, retrosplenial and temporal cortices after generalized seizures. The magnitude of the increases was similar throughout the development of kindling and in the fully kindled brain. No changes of trkA messenger RNA were observed. In amygdalar kindling, elevated brain-derived neurotrophic factor messenger RNA levels developed more rapidly in the amygdala-piriform cortex than after stimulation in the hippocampus but changes in the hippocampal formation were only seen in few animals. Intraventricular 6-hydroxydopamine or a bilateral fimbria-fornix lesion did not alter basal expression or seizure-evoked changes in messenger RNA levels for neurotrophins or trk receptors but increased the number of animals exhibiting elevated levels after the first stimulation, probably due to a prolongation of seizure activity. Both in sham-operated and fimbria-fornix-lesioned rats seizure activity caused a marked reduction of neurotrophin-3 messenger RNA levels in dentate granule cells. The results indicate that activation of the brain-derived neurotrophic factor gene, at least in dentate granule cells, is an "all-or-none" type of response and dependent on the duration but not the severity of seizures or the stage of kindling epileptogenesis. Changes in brain-derived neurotrophic factor, nerve growth factor, neurotrophin-3 and trkB and trkC were observed concomitantly in the dentate gyrus, which suggests that seizure activity sets in motion a cascade of genomic events possibly mediated via a common mechanism. Since altered messenger RNA levels outside hippocampus were detected only for brain-derived neurotrophic factor, neurotrophin and trk gene expression in these regions seems to be regulated differently.