Hippocampal cannabinoid-1 receptor upregulation upon endothelin-B receptor deficiency: a neuroprotective substitution effect?

Endothelin (ETB)-receptors mediate anti-apoptotic actions. Lack of functional ETB-receptors leads to increased neuronal apoptosis in the hippocampus. The increased apoptosis must be compensated by other mechanisms, however, as ETB-deficient rats display normal overall brain morphology. To illuminate on brain plasticity in ETB-receptor deficiency, we studied the expression and function of another neuroprotective system, the cannabinoid CB1-receptors, in ETB-deficient hippocampus. We show that CB1 expression in hippocampus increases postnatally in all rats but that the increase in CB1-receptor expression is significantly higher in ETB-deficient compared to wildtype littermates. Neuronal apoptosis decreases during brain maturation but remains on a significantly higher level in the ETB-deficient compared to wildtype dentate. When investigating survival of hippocampal neurons in culture, we found significant protection against hypoxia-induced cell death with CB1-analogs (noladin, (9-tetrahydrocannabinol) only in ETB-deficient neurons. We suggest that CB1-receptor upregulation in the ETB-mutant hippocampus reflects an attempt to compensate for the lack of ETB-receptors.

Complications after cryosurgery with new miniature cryoprobes in long hollow bones: an animal trial.

BACKGROUND: In vitro studies show that new miniature cryoprobes are suitable for cryoablation of bone tissue. The aim of this animal trial on 24 sheep was to examine the perioperative complications, particularly the danger of embolism, of cryoablation when using miniature cryoprobes. METHODS: Cryoablations with 2 freeze-thaw cycles each were carried out in the epiphysis of the right tibia and the metaphysis of the left femur. Pulmonary artery pressure (PAP) and central venous pressure (CVP) were measured. Throughout the intra- and perioperative phase, heart rate and oxygen saturation by pulse oxymetry, blood gas and electrolytes were monitored regularly. Postoperative complications were examined up to 24 weeks postoperative. RESULTS: As result, no significant increase of PAP, CVP or heart rate were observed. Blood gases were unremarkable, with pO2 and pCO2 remaining constant throughout the operation. Regarding pH, standard bicarbonate and base excess, only a non-significant shift towards a slight acidosis was seen. There was a mean hemoglobin decrease of 0.5 g/dl. One animal showed postoperative wound infection and wound edge necrosis. No major peri- and postoperative complications associated with cryosurgery of bone were observed, especially regarding clinically relevant pulmonary embolism. CONCLUSION: Surgery with new types of miniature cryoprobes appears to be a safe alternative to or a complement to conventional resection of abnormal bone tissue.

The use of a new miniature cryoprobe for ablation of bone tissue: in vivo assessment of the probe and application of the method to bone in a sheep model.

BACKGROUND: So far, modern miniature cryoprobes were used for local destruction of soft tissue tumours without damaging the adjacent healthy tissue. In this study, cryoablation methodology was applied to bone and the cooling capacity of the probe was examined in vitro and in vivo. METHOD: Freezing was performed by cooling one or two probes (diameter 3.2 mm) to -180 degrees C with liquid nitrogen. The cooling capacity of the probes was determined optically and thermally against a homogeneous reference gel, followed by in vivo measurements on femoral and tibial sheep bone followed by histological examination. RESULTS: Thanks to the synergistic effect, the simultaneous use of 2 probes produced an almost spherical expansion of cold in the homogenous gelatin. During the in vivo freezes, the temperature curves showed a more moderate trend. Nevertheless, due to the synergistic effect, temperatures below -50 degrees C could be reached at a distance of 1 cm from the probe. No local or systemic intraoperative complications were observed. Histological examination revealed cell necrosis up into the -10 degrees C isotherm. CONCLUSIONS: Adequate tissue cooling of the bone matrix can be achieved with in vivo freezes by means of one or more miniature cryoprobes. Therefore, this probe could provide an alternative to or supplement surgical resection of pathological bone processes.

Comparison of long-term outcomes of myomectomy and uterine artery embolization.

OBJECTIVE: To compare long-term outcomes of uterine artery embolization and abdominal myomectomy in patients with symptomatic uterine myomas. METHODS: At a single institution in an 18-month time, 59 patients had bilateral uterine artery embolization and 38 patients had abdominal myomectomy to treat symptomatic uterine myomas. We reviewed medical records and surveyed patients 3 or more years after their procedures to assess how many needed further surgical procedures in the intervening years, to what extent symptoms remained improved, and how satisfied the patients were with the long term results of the index procedure. RESULTS: Follow-up was available on 51 embolization and 30 myomectomy patients and ranged from 37 to 59 months. Patients who had embolization were older (44 versus 38 years, P <.001) and more likely to have had previous surgical procedures (P <.001) than those who had myomectomy. Taking into account the variable follow-up period, embolization patients were more likely to have had further invasive treatment for myomas (29% versus 3%) (P =.004). Among women not needing further surgery, overall symptoms improved in 92% (33/36) of embolization and 90% (26/29) of myomectomy patients (P =.78). Ninety-four percent (34/36) of embolization patients and 79% (23/29) of myomectomy patients were at least somewhat satisfied with their choice of procedure (P =.06). CONCLUSION: Women who had embolization were more likely than those who had myomectomy to need further invasive treatment (surgery or repeat embolization) in the 3-5 years after the index procedure. Among women who did not need such treatment, satisfaction and relief of symptoms were similar. Large, randomized trials are needed to more accurately compare these two procedures.

Autoimmune hepatitis and overlap syndromes.

Autoimmune hepatitis (AIH) is an immune-mediated, autodestructive liver disease with hepatocytes as target cells, mostly affecting young women. Primary biliary cirrhosis (PBC) is also regarded as an autoimmune liver disease with bile duct epithelia as the target cells, resulting in a continuous loss of bile ducts. Both diseases may occur simultaneously in their full manifestations in about 10% to 20% of cases, thus constituting an overlap syndrome with PBC directing the course of the disease. AIH may also occur simultaneously with primary sclerosing cholangitis (PSC), with a frequency of between 2% and 8% of patients with PSC. In most cases, AIH precedes manifestation of PSC. In children, the overlap syndrome of AIH and PSC seems to make up an entity of its own: autoimmune sclerosing cholangitis.