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Sound information is transduced into graded receptor potential by cochlear hair cells and encoded as discrete action potentials of auditory nerve fibers. In the cochlear nucleus, auditory nerve fibers convey this information through morphologically distinct synaptic terminals onto bushy cells (BCs) and stellate cells (SCs) for processing of different sound features. With expanding use of transgenic mouse models, it is increasingly important to understand the in vivo functional development of these neurons in mice. We characterized the maturation of spontaneous and acoustically evoked activity in BCs and SCs by acquiring single-unit juxtacellular recordings between hearing onset (P12) and young adulthood (P30) of anesthetized CBA/J mice. In both cell types, hearing sensitivity and characteristic frequency (CF) range are mostly adult-like by P14, consistent with rapid maturation of the auditory periphery. In BCs, however, some physiological features like maximal firing rate, dynamic range, temporal response properties, recovery from post-stimulus depression, first spike latency (FSL) and encoding of sinusoid amplitude modulation undergo further maturation up to P18. In SCs, the development of excitatory responses is even more prolonged, indicated by a gradual increase in spontaneous and maximum firing rates up to P30. In the same cell type, broadly tuned acoustically evoked inhibition is immediately effective at hearing onset, covering the low- and high-frequency flanks of the excitatory response area. Together, these data suggest that maturation of auditory processing in the parallel ascending BC and SC streams engages distinct mechanisms at the first central synapses that may differently depend on the early auditory experience.

Amyloid beta (Aβ)-mediated synapse dysfunction and spine loss are considered to be early events in Alzheimer's disease (AD) pathogenesis. N-methyl-D-aspartate receptors (NMDARs) have previously been suggested to play a role for Amyloid beta (Aβ) toxicity. Pharmacological block of NMDAR subunits in cultured neurons and mice suggested that NMDARs containing the GluN2B subunit are necessary for Aβ-mediated changes in synapse number and function in hippocampal neurons. Interestingly, NMDARs undergo a developmental switch from GluN2B- to GluN2A-containing receptors. This indicates different functional roles of NMDARs in young mice compared to older animals. In addition, the lack of pharmacological tools to efficiently dissect the role of NMDARs containing the different subunits complicates the interpretation of their specific role. In order to address this problem and to investigate the specific role for Aβ toxicity of the distinct NMDAR subunits in dentate gyrus granule cells of adult mice, we used conditional knockout mouse lines for the subunits GluN1, GluN2A and GluN2B. Aβ-mediated changes in synaptic function and neuronal anatomy were investigated in several-months old mice with virus-mediated overproduction of Aβ and in 1-year old 5xFAD mice. We found that all three NMDAR subunits contribute to the Aβ-mediated decrease in the number of functional synapses. However, NMDARs are not required for the spine number reduction in dentate gyrus granule cells after chronic Aβ-overproduction in 5xFAD mice. Furthermore, the amplitude of synaptic and extrasynaptic NMDAR-mediated currents was reduced in dentate gyrus granule of 5xFAD mice without changes in current kinetics, suggesting that a redistribution or change in subunit composition of NMDARs does not play a role in mediating Amyloid beta (Aβ) toxicity. Our study indicates that NMDARs are involved in AD pathogenesis by compromising synapse function but not by affecting neuron morphology.

Living kidney donation is safe and established, but can lead to long-term complications such as chronic fatigue. Since the adrenal vein is usually transected during left-sided donor nephrectomy-which is not necessary on the right-we hypothesized that venous congestion might lead to an impairment of adrenal function, offering a possible explanation. In this prospective open label, monocentric cohort study, adrenal function was compared in left- and right-sided living kidney donors. The primary endpoint was plasma cortisol response to low-dose adrenocorticotropic hormone (ACTH) stimulation. Secondary endpoints included plasma renin and ACTH concentration as well as adrenal volume in response to donor nephrectomy. A total of 30 healthy donors-20 left- and 10 right-sided donations-were included. On postoperative day 1, response to low-dose ACTH stimulation was intact, but significantly lower after left-sided donor nephrectomy. After 28 days, adrenal responsiveness to ACTH stimulation did not differ any longer. Magnetic resonance imaging volumetry showed no significant adrenal volume change over 4 weeks, neither after left- nor after right-sided nephrectomy. In conclusion, left-sided living kidney donation entails a transiently reduced adrenocortical responsiveness, which returns to baseline after 28 days., (© 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.)

N-methyl-D-aspartate receptors (NMDARs) in all hippocampal areas play an essential role in distinct processes of memory formation as well as in sustaining cell survival of postnatally generated neurons in the dentate gyrus (DG). In contrast to the beneficial effects, over-activation of NMDARs has been implicated in many acute and chronic neurological diseases, reason why therapeutic approaches and clinical trials involving receptor blockade have been envisaged for decades. Here we employed genetically engineered mice to study the long-term effect of NMDAR ablation on selective hippocampal neuronal populations. Ablation of either GluN1 or GluN2B causes degeneration of the DG. The neuronal demise affects mature neurons specifically in the dorsal DG and is NMDAR subunit-dependent. Most importantly, the degenerative process exacerbates with increasing age of the animals. These results lead us to conclude that mature granule cells in the dorsal DG undergo neurodegeneration following NMDAR ablation in aged mouse. Thus, caution needs to be exerted when considering long-term administration of NMDAR antagonists for therapeutic purposes.

Background: In the field of anesthesia for bariatric surgery, a wide variety of recommendations exist, but a general consensus on the perioperative management of such patients is missing. We outline the perioperative experiences that we gained in the first two years after introducing a bariatric program., Methods: The perioperative approach was established together with all relevant disciplines. Pertinent topics for the anesthesiologists were; successful airway management, indications for more invasive monitoring, and the planning of the postoperative period and deposition. This retrospective analysis was approved by the local ethics committee. Data are mean [SD]., Results: 182 bariatric surgical procedures were performed (147 gastric bypass procedures (GBP; 146 (99.3%) performed laparascopically). GBP patients were 43 [10] years old, 78% female, BMI 45 [7] kg/m(2), 73% ASA physical status of 2. 42 patients (28.6%) presented with obstructive sleep apnea syndrome. 117 GBP (79.6%) patients were intubated conventionally by direct laryngoscopy (one converted to fiber-optic intubation, one aspiration of gastric contents). 32 patients (21.8%) required an arterial line, 10 patients (6.8%) a central venous line. Induction lasted 25 [16] min, the procedure itself 138 [42] min. No blood products were required. Two patients (1.4%) presented with hypothermia (<35 °C) at the end of their case. The emergence period lasted 17 [9] min. Postoperatively, 32 patients (21.8%) were transferred to the ICU (one ventilated). The other patients spent 4.1 [0.7] h in the post anesthesia care unit. 15 patients (10.2%) required take backs for surgical revision (two laparotomies)., Conclusions: The physiology and anatomy of bariatric patients demand a tailored approach from both the anesthesiologist and the perioperative team. The interaction of a multi-disciplinary team is key to achieving good outcomes and a low rate of complications., Trial Registration: DRKS00005437 (date of registration 16(th) December 2013).

Clinical features, myelography, and computed tomography imaging findings as well as neurological outcome with and without surgery in 5 pug dogs with thoracolumbar arachnoid diverticula are described. Short-term prognosis after surgical therapy may not be as good as reported for other canine breeds, since immediate postsurgical deterioration is possible. Improvement of neurological deficits beyond the presurgical status may take several months.

Introduction: Vertical-banded gastroplasty, a technique that is commonly performed in the treatment of morbid obesity, represents a nonadjustable restrictive procedure which reduces the volume of the upper stomach by a vertical stapler line. In addition, a textile or silicone band restricts food passage through the stomach., Case Presentation: A 71-year-old woman presented with a severe gastric stenosis 11 years after vertical gastroplasty. We describe a side-to-side gastrogastrostomy as a safe surgical procedure to restore the physiological gastric passage after failed vertical-banded gastroplasty., Conclusion: Occasionally, restrictive procedures for morbid obesity cannot be converted into an alternative bariatric procedure to maintain weight control. This report demonstrates that a side-to-side gastrogastrostomy is a feasible and safe procedure.

Gastric acid secretion is activated by two distinct pathways: a neuronal pathway via the vagus nerve and release of acetylcholine and an endocrine pathway involving gastrin and histamine. Recently, we demonstrated that activation of H(+)-K(+)-ATPase activity in parietal cells in freshly isolated rat gastric glands is modulated by the calcium-sensing receptor (CaSR). Here, we investigated if the CaSR is functionally expressed in freshly isolated gastric glands from human patients undergoing surgery and if the CaSR is influencing histamine-induced activation of H(+)-K(+)-ATPase activity. In tissue samples obtained from patients, immunohistochemistry demonstrated the expression in parietal cells of both subunits of gastric H(+)-K(+)-ATPase and the CaSR. Functional experiments using the pH-sensitive dye 2',7'-bis-(2-carboxyethyl)-5-(and 6)-carboxyfluorescein and measurement of intracellular pH changes allowed us to estimate the activity of H(+)-K(+)-ATPase in single freshly isolated human gastric glands. Under control conditions, H(+)-K(+)-ATPase activity was stimulated by histamine (100 microM) and inhibited by omeprazole (100 microM). Reduction of the extracellular divalent cation concentration (0 Mg(2+), 100 microM Ca(2+)) inactivated the CaSR and reduced histamine-induced activation of H(+)-K(+)-ATPase activity. In contrast, activation of the CaSR with the trivalent cation Gd(3+) caused activation of omeprazole-sensitive H(+)-K(+)-ATPase activity even in the absence of histamine and under conditions of low extracellular divalent cations. This stimulation was not due to release of histamine from neighbouring enterochromaffin-like cells as the stimulation persisted in the presence of the H(2) receptor antagonist cimetidine (100 microM). Furthermore, intracellular calcium measurements with fura-2 and fluo-4 showed that activation of the CaSR by Gd(3+) led to a sustained increase in intracellular Ca(2+) even under conditions of low extracellular divalent cations. These experiments demonstrate the presence of a functional CaSR in the human stomach and show that this receptor may modulate the activity of acid-secreting H(+)-K(+)-ATPase in parietal cells. Furthermore, our results show the viability of freshly isolated human gastric glands and may allow the use of this preparation for experiments investigating the physiological regulation and properties of human gastric glands in vitro.

Objective: To define whether laparoscopic gastric banding or laparoscopic Roux-en-Y gastric bypass represents the better approach to treat patients with morbid obesity., Summary Background Data: Two techniques, laparoscopic gastric bypass or gastric banding, are currently widely used to treat morbid obesity. Since both procedures offer certain advantages, a strong controversy exists as to which operation should be proposed to these patients. Therefore, data are urgently needed to identify the best therapy., Methods: Since randomized trials are most likely not feasible because of the highly different invasiveness and irreversibility of these procedures, a matched-pair design of a large prospectively collected database appears to be the best method. Therefore, we used our prospective database including 678 bariatric procedures performed at our institution since 1995. A total of 103 consecutive patients with laparoscopic gastric bypass were randomly matched to 103 patients with laparoscopic gastric banding according to age, body mass index, and gender., Results: Both groups were comparable regarding age, gender, body mass index, excessive weight, fat mass, and comorbidites such as diabetes, heart disease, and hypertension. Feasibility and safety: All gastric banding procedures were performed laparoscopically, and one gastric bypass operation had to be converted to an open procedure. Mean operating time was 145 minutes for gastric banding and 190 minutes for gastric bypass (P < 0.001). Hospital stay was 3.3 days for gastric banding and 8.4 days for gastric bypass. The incidence of early postoperative complications was not significantly different, but late complications were significantly more frequent in the gastric banding group (pouch dilatation). There was no mortality in both groups. Efficiency: Body mass index decreased from 48.0 to 36.8 kg/m in the gastric banding group and from 47.8 to 31.9 kg/m in the gastric bypass group within 2 years of surgery. These differences became significant from the first postoperative month until the end of the follow-up (24 months). The gastric bypass procedure achieved a significantly better reduction of comorbidities., Conclusions: Laparoscopic gastric banding and laparoscopic gastric bypass are feasible and safe. Pouch dilatations after gastric banding are responsible for more late complications compared with the gastric bypass. Laparoscopic gastric bypass offers a significant advantage regarding weight loss and reduction of comorbidities after surgery. Therefore, in our hands, laparoscopic Roux-en-Y gastric bypass appears to be the therapy of choice.

Objective: To define whether laparoscopic rebanding or Roux-en-Y gastric bypass represents the best approach for failed laparoscopic gastric banding in patients with morbid obesity., Summary Background Data: Countless laparoscopic gastric bandings have been implanted during the recent years worldwide. Despite excellent short-term results, long-term failures and complications have been reported in more than 20% of patients. Which rescue procedures should be used remains controversial. Therefore, we analyzed our experience with the use of laparoscopic rebanding versus laparoscopic Roux-en-Y gastric bypass after failed gastric banding., Methods: Using a prospectively collected database, we analyzed the feasibility, safety, and effectiveness of laparoscopic rebanding versus laparoscopic conversion to Roux-en-Y gastric bypass after failed laparoscopic gastric banding. RESULTS A total of 62 consecutive patients were treated in our institution between May 1995 and December 2002 for failed primary laparoscopic gastric banding, including 30 laparoscopic rebandings and 32 laparoscopic conversions to Roux-en-Y gastric bypass. Rebandings were preferably done during the initial period of the study and Roux-en-Y gastric bypass in the last period. Both groups were comparable before the initial banding procedures. At the time of redo surgery, patients receiving a gastric bypass had more esophageal dysmotility (47% vs. 7%, P = 0.002) and higher body mass index (BMI) than those elected for rebanding procedures (BMI 42.0 vs. 38.4 kg/m2, P = 0.015). Feasibility and safety: Each procedure was performed laparoscopically. Mean operating time was 215 minutes for gastric bypass and 173 minutes for rebanding (P = 0.03). Early complications occurred in one case in the rebanding group and in 2 cases in the bypass group; all underwent a laparoscopic reexploration without the need for open surgery. There was no mortality in this series. Effectiveness: BMI in the gastric bypass group decreased from 42.0 to 31.8 kg/m2 (P = 0.02) within 1 year of surgery, while it remained unchanged in the rebanding group., Conclusions: Laparoscopic conversion to a gastric bypass as well as laparoscopic rebanding are feasible and safe. Conversion to gastric bypass offers a significant advantage in terms of further weight loss after surgery. Therefore, this procedure should be considered as the rescue therapy of choice after a failed laparoscopic gastric banding.

Silymarin can be extracted from the milk thistle, and silibinin is the main component of the plant extract. Possibly due to their antioxidant and membrane-stabilizing properties, the compounds have been shown to protect different organs and cells against a number of insults. Thus liver, kidney, erythrocytes and platelets have been protected from the toxic effects of ethanol, carbon tetrachloride, cold ischemia and drugs, respectively. The effect of silibinin on endocrine and exocrine pancreas, however, has not been studied. We therefore investigated whether silibinin treatment attenuates cyclosporin A (CiA) toxicity on rat endocrine and exocrine pancreas. Groups of 15 male Wistar rats were treated for 8 days with CiA and/or silibinin. On day 9, endocrine and exocrine pancreatic functions were tested in vitro. At the end of the treatment period, blood glucose levels in vivo were significantly higher in rats treated with CiA while silibinin did not affect glucose levels. In vitro, insulin secretion was inhibited after treatment with silibinin, but amylase secretion was not affected. After treatment with CiA both insulin and amylase secretion were reduced. Silibinin and CiA had an additive inhibitory effect on insulin secretion, but silibinin attenuated CiA-induced inhibition of amylase secretion. Despite CiA treatment, amylase secretion was in fact restored to normal with the highest dose of silibinin. Thus silibinin inhibits glucose-stimulated insulin release in vitro, while not affecting blood glucose concentration in vivo. This combination of effects could be useful in the treatment of non-insulin-dependent diabetes mellitus. Furthermore, silibinin protects the exocrine pancreas from CiA toxicity. As this inhibitory effect is probably unspecific, silibinin may also protect the exocrine pancreas against other insult principles, such as alcohol.

Somatostatin is a potent inhibitor of endocrine and exocrine pancreatic secretion. However, it is not clear whether it also inhibits pancreatic growth. Therefore we treated male Wistar rats with a somatostatin analogue, octreotide (12-192 micrograms/(kg body wt.day)), over a period of 14 days. In a dose-dependent manner, this potent and long-acting analogue caused a reduction in weight of the pancreas and a reduction in pancreatic content of protein, DNA, trypsin, chymotrypsin, amylase and lipase, as well as pancreatic content of insulin-, glucagon- and somatostatin-like immunoreactivities. When growth of rat pancreas was induced by oral administration of camostate (200 mg/(kg body wt. day) or by subcutaneous administration of cholecystokinin (2 x 10 micrograms/(kg body wt. day)) over a period of 14 days, octreotide (12-192 micrograms/(kg body wt.day)) had the same effects, but these were even more pronounced. We conclude that somatostatin is an important regulator of pancreatic growth.

Previous work has shown that cyclosporin A is toxic to the endocrine and exocrine pancreas. The aim of this study was to examine whether endogenous eicosanoids play a role in controlling cyclosporin A induced toxicity. Rats were treated for eight days with indomethacin (2 mg/kg, twice daily) in addition to cyclosporin A (5 or 10 mg/kg daily). Effects of drug treatments on exocrine (as assessed by amylase and protein secretion into the pancreatic juice) and endocrine (as assessed by the glucose dependent insulin release) pancreatic functions, and pancreatic formation of prostaglandins and thromboxane were evaluated. Treatment with cyclosporin A in the doses used did not inhibit eicosanoid formation by the pancreatic tissue ex vivo. Indomethacin caused significant inhibition of pancreatic formation of prostaglandin E2, 6k prostaglandin F1 alpha and thromboxane B2. Combined treatment with indomethacin and cyclosporin A (5 or 10 mg/kg) augmented cyclosporin A induced pancreatic toxicity with further impairment of insulin release, amylase secretion, and pancreatic juice protein content, but did not result in more pronounced inhibition of pancreatic eicosanoid formation. The increased toxicity of the combined treatment was, however, associated with raised cyclosporin A whole blood concentrations. The data suggest that the potentiation of pancreatic toxicity of cyclosporin A observed during coadministration of indomethacin is not the result of suppression of endogenous pancreatic eicosanoid biosynthesis, but more likely results from altered cyclosporin A pharmacokinetic which may be caused by an interference of indomethacin with the hepatic cytochrome P-450 dependent monooxygenase involved in cyclosporin A metabolism. The possibility that coadministration of non-steroidal antiinflammatory drugs aggravates toxic effects in cyclosporin A treated patients should be considered.

Cyclosporin 5, 10, and 20 mg/kg bw was given to rats once daily intragastrically and caused a dose dependent, significant decrease of glucose dependent insulin release from the arterially perfused isolated pancreas, without affecting animal behaviour, weight gain, microscopic appearances of the pancreas, or kidney function. Subcutaneous injection of a new synthetic prostaglandin analogue Rioprostil 7.5 micrograms/kg bw twice daily completely prevented the effect of cyclosporin 5 mg/kg bw and protected significantly against the effects of cyclosporin 10 and 20 mg/kg bw.