Restoration of Serotonin Neuronal Firing Following Long-Term Administration of Bupropion but Not Paroxetine in Olfactory Bulbectomized Rats

Background:

Olfactory bulbectomized rats generally manifest many of the neurochemical, physiological, and behavioral features of major depressive disorder in humans. Another interesting feature of this model is that it responds to chronic but not acute antidepressant treatments, including selective serotonin reuptake inhibitors. The purpose of the present study was first to characterize the firing activity of dorsal raphe serotonin neurons in olfactory bulbectomized rats and then examine the effects of 2 antidepressants, bupropion and paroxetine.

Methods:

Olfactory bulbectomy was performed by aspirating olfactory bulbs in anesthetized rats. Vehicle and drugs were delivered for 2 and 14 days via subcutaneously implanted minipumps. In vivo electrophysiological recordings were carried out in male anesthetized Sprague-Dawley rats.

Results:

Following ablation of olfactory bulbs, the firing rate of serotonin neurons was decreased by 36%, leaving those of norepinephrine and dopamine neurons unchanged. In olfactory bulbectomized rats, bupropion (30mg/kg/d) restored the firing rate of serotonin neurons to the control level following 2- and 14-day administration and also induced an increase in the tonic activation of serotonin_1A receptors; paroxetine (10mg/kg/d) did not result in a return to normal of the attenuated firing of serotonin neurons in olfactory bulbectomized rats. In the hippocampus, although at a higher dose of WAY 100635 than that required in bupropion-treated animals, paroxetine administration also resulted in an increase in the tonic activation of serotonin_1A receptors.

Conclusions:

The present results indicate that unlike paroxetine, bupropion administration normalized serotonin neuronal activity and increased tonic activation of the serotonin_1A receptors in hippocampus.     

Tacrolimus (FK 506), a Treatment for Primary Sclerosing Cholangitis: Results of an Open-Label Preliminary Trial

Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease of the liver that is characterized by progressive cholestasis and the development of secondary biliary cirrhosis. There is no widely recognized therapy for this disease, although anti-inflammatory agents (steroids), immunosuppressive agents (methotrexate), anti-fihrotics (colchicine), and choleretic agents (ursodeoxycholic acid) have been used in various small series. In the present study, Tacrolimus (FK 506), a new and powerful immunosuppressive macrolide antibiotic, has been used to treat 10 patients with PSC. Each subject had a liver biopsy, ERCP with visualization of the intra-and extrahepatic biliary tree, and a panel of hcmatological, serological, and biochemical laboratory tests before the initiation of the FK 506 therapy. The FK 506 was administered orally at 12-h intervals and was monitored by serial plasma FK 506 trough levels. After 360 days of treatment, the median serum bilirubin level was reduced by 75%, and the serum alkaline phosphatase was reduced by 70%. Moreover, the serum ALT and AST levels were reduced by 80 and 86%, respectively. No change in the serum level of BUN and creatinine levels occurred as a consequence of the FK 506 treatment. These data demonstrate that: 1) FK 506 can be used to treat PSC; 2) the response to FK 506 by patients with PSC is rapid; and, 3) no adverse effect on the serum BUN and creatinine levels was observed. It is anticipated that FK 506 will become an important agent for the treatment of patients with PSC because of its powerful immunosuppressive activity.     

Prevalence,morphology, and molecular analysis of Serrasentis sagittifer (Acanthocephala: Palaeacanthocephala: Rhadinorhynchidae), a parasite of the gilthead Sea bream Sparus aurata (Sparidae)

Seventy specimens of the gilthead sea bream Sparus aurata of the Red Sea were collected during the period from March to November 2013; they were dissected and examined for parasitic acanthocephalans. Only 40 (57.14 %) specimens were found to be naturally infected with Serrasentis sagittifer belonging to family Rhadinorhynchidae. The infection was recorded in the intestine, pyloric ceca, and the external surfaces of some internal organs of the infected fish. Seasonally, the prevalence of infection was increased to 77.14 % during summer season and decreased to 37.14 % during winter. Light and scanning electron microscopic investigation revealed that the adult worm was elongated (with broad anterior and narrow posterior ends) and measured 6.9–8.6 (7.6?±?0.2)?×?0.57–0.73 (0.63?±?0.02) mm for male and 10.2–12.1 (11.5?±?0.2)?×?0.71–0.82 (0.76?±?0.02) mm for female. Proboscis was long and cylindrical with a length of 0.97–1.6 mm (1.2?±?0.2) for male and 1.12–1.17 mm (1.14?±?0.02) for female. It was covered with numerous uniform spines arranged longitudinally as 9–11 rows each equipped by 15–18 spines. Spines were triangular, arrow-shaped, strong, and covered with cuticular theca; they decreased in size from the apex to the base of the proboscis. The proboscis is followed by a short spineless neck region followed by the body proper which is supported by multiple combs of spines (16–20) on its ventral surface. Molecular analysis of 18S rDNA sequence for the parasite demonstrated a close identity (>83 %) between the present acanthocephalan and other previously described species within class Palaeacanthocephala with 98 % identity with the previously recorded S. sagittifer (acc. no. JX014227) which is supported by the morphological data and the presence of trunk spines arranged within rows (comb-like) and the presence of four cement glands in the males. So, according to the records of morphological and molecular analyses, the present parasite is classified as S. sagittifer belonging to class Palaeacanthocephala and family Rhadinorhynchidae with a new host record from the gilthead sea bream S. aurata of the Red Sea.     

Distributed optimal control of viscous Burgers' equation via a high-order,linearization, integral,nodal discontinuous Gegenbauer-Galerkin method

We developed a novel direct optimization method to solve distributed optimal control of viscous Burgers' equation over a finite-time horizon by minimizing the distance between the state function and a desired target state profile along with the energy of the control. Through a novel linearization strategy, well-conditioned integral reformulations, optimal Gegenbauer barycentric quadratures, and nodal discontinuous Galerkin discretizations, the method reduces such optimal control problems into finite-dimensional, nonlinear programming problems subject to linear algebraic system of equations and discrete mixed path inequality constraints that can be solved easily using standard optimization software. The proposed method produces “an auxiliary control function” that provides a useful model to explicitly define the optimal controller of the state variable. We present an error analysis of the semidiscretization and full discretization of the weak form of the reduced equality constraint system equations to demonstrate the exponential convergence of the method. The accuracy of the proposed method is examined using two numerical examples for various target state functions in the existence/absence of control bounds. The proposed method is exponentially convergent in both space and time, thus producing highly accurate approximations using a significantly small number of collocation points.     

India’s first successful intestinal transplant: The road traveled and the lessons learnt

Intestinal transplant is a therapeutic challenge not just surgically but also logistically because of the multidisciplinary expertise and resources required. A large proportion of patients who undergo massive bowel resection and develop intestinal failure have poor outcome, because of inability to sustain long-term parenteral nutrition and limited availability of intestinal and multi-visceral transplantation facilities. We report the first successful isolated intestinal transplant from India.