Reversal of haloperidol-induced tardive vacuous chewing movements and supersensitive somatodendritic serotonergic response by buspirone in rats

Tardive dyskinesia (TD), a syndrome of involuntary hyperkinesias in the orofacial region that develops in patients chronically treated with neuroleptic agents is a major limitation of the therapy. Rats chronically treated with haloperidol exhibit vacuous chewing movements (VCMs) with the twitching of facial musculature and tongue protrusion. The syndrome is widely used as an animal model of TD. Evidence suggests a role of 5-hydroxytryptamine (5-HT; serotonin)-1A receptors in the pathogenesis and treatment of TD because repeated administration of haloperidol resulted in an increase in the effectiveness of 5-HT-1A receptors while drugs with agonist activity at 5-HT-1A receptors could attenuate haloperidol-induced VCMs. The present study was designed to test the hypothesis that a decrease in the responsiveness of somatodendritic 5-HT-1A receptors by the coadministration of buspirone could reverse the induction of VCMs and supersensitivity at 5-HT-1A receptors by haloperidol. Rats treated with haloperidol at a dose of 1 mg/kg twice a day for 2 weeks displayed VCMs with twitching of facial musculature that increased in a time dependent manner as the treatment continued to 5 weeks. Coadministration of buspirone attenuated haloperidol-induced VCMs after 2 weeks and completely prevented it after 5 weeks. The intensity of 8-hydroxy-2-di (n-propylamino) tetralin (8-OH-DPAT)-induced locomotion was greater in saline+haloperidol injected animals but not in buspirone+haloperidol injected animals. 8-OH-DPAT-induced decreases of 5-HT metabolism were greater in saline+haloperidol injected animals but not in buspirone+haloperidol injected animals. It is suggested that an impaired somatodendritic 5-HT-1A receptor dependent response is a major contributing factor in the pathophysiology of TD and a normalization of the somatodendritic response by drugs may help extending therapeutics in schizophrenia.     

Intelligent optimal control with dynamic neural networks.

The application of neural networks technology to dynamic system control has been constrained by the non-dynamic nature of popular network architectures. Many of difficulties are-large network sizes (i.e. curse of dimensionality), long training times, etc. These problems can be overcome with dynamic neural networks (DNN).In this study, intelligent optimal control problem is considered as a nonlinear optimization with dynamic equality constraints, and DNN as a control trajectory priming system. The resulting algorithm operates as an auto-trainer for DNN (a self-learning structure) and generates optimal feed-forward control trajectories in a significantly smaller number of iterations. In this way, optimal control trajectories are encapsulated and generalized by DNN. The time varying optimal feedback gains are also generated along the trajectory as byproducts. Speeding up trajectory calculations opens up avenues for real-time intelligent optimal control with virtual global feedback.We used direct-descent-curvature algorithm with some modifications (we called modified-descend-controller-MDC algorithm) for the optimal control computations. The algorithm has generated numerically very robust solutions with respect to conjugate points. The adjoint theory has been used in the training of DNN which is considered as a quasi-linear dynamic system. The updating of weights (identification of parameters) are based on Broyden-Fletcher-Goldfarb-Shanno BFGS method. Simulation results are given for an intelligent optimal control system controlling a difficult nonlinear second-order system using fully connected three-neuron DNN.     

Sezary syndrome--without erythroderma

Sezary syndrome (SS), is described as the classical triad of pruritic erythroderma, lymphadenopathy, and presence of more than 10% of circulating Sezary cells in the peripheral blood. We report on unusual case of advanced cutaneous T - cell lymphoma with classical haematological and histopathological features of Sezary syndrome, but lacking the clinical features of erythroderma. A 66 year old man presented with asymptomatic multiple papules, plaques and nodules and with generalized lymphadenopathy. Peripheral smear showed more than 60% of Sezary cells. Skin and lymph node biopsy showed typical features of T-cell lymphoma and immunohistochemistry and CD marker studies showed the cells to be atypical T-lymphocytes. This unusual case is highlighted to denote that erythroderma need not be taken as a hard and fast criterion for diagnosing Sezary syndrome.     

Liposomal drug delivery systems: an update review

The discovery of liposome or lipid vesicle emerged from self forming enclosed lipid bi-layer upon hydration; liposome drug delivery systems have played a significant role in formulation of potent drug to improve therapeutics. Recently the liposome formulations are targeted to reduce toxicity and increase accumulation at the target site. There are several new methods of liposome preparation based on lipid drug interaction and liposome disposition mechanism including the inhibition of rapid clearance of liposome by controlling particle size, charge and surface hydration. Most clinical applications of liposomal drug delivery are targeting to tissue with or without expression of target recognition molecules on lipid membrane. The liposomes are characterized with respect to physical, chemical and biological parameters. The sizing of liposome is also critical parameter which helps characterize the liposome which is usually performed by sequential extrusion at relatively low pressure through polycarbonate membrane (PCM). This mode of drug delivery lends more safety and efficacy to administration of several classes of drugs like antiviral, antifungal, antimicrobial, vaccines, anti-tubercular drugs and gene therapeutics. Present applications of the liposomes are in the immunology, dermatology, vaccine adjuvant, eye disorders, brain targeting, infective disease and in tumour therapy. The new developments in this field are the specific binding properties of a drug-carrying liposome to a target cell such as a tumor cell and specific molecules in the body (antibodies, proteins, peptides etc.); stealth liposomes which are especially being used as carriers for hydrophilic (water soluble) anticancer drugs like doxorubicin, mitoxantrone; and bisphosphonate-liposome mediated depletion of macrophages. This review would be a help to the researchers working in the area of liposomal drug delivery.     

Topical corticosteroids in psoriasis: strategies for improving safety

Corticosteroids are a mainstay of topical therapy for psoriasis. While efficacious and relatively safe when used carefully, the potential for side effects, notably skin atrophy and adrenal suppression, have been associated with excesses in potency, prolonged or widespread use. The International Psoriasis Council Working Group on Topical Therapy has reviewed the efficacy and safety of topical corticosteroids and recommends strategies for safe, long‐term use of these agents.     

Radiocontrast-induced nephropathy in a pair of xiphaomphalopagus conjoined twins during the neonatal period

One of the babies in a pair of xiphaomphalopagus conjoined twins developed oliguria, transient rise in serum creatinine and persistent nephrogram on the sixth day of life following injection of radiocontrast medium for computerised axial tomography scanning of the urinary system. The other twin was spared but developed hypertension and "dialysed" the oliguric twin. The renal profiles of both neonates subsequently remained normal until they reached adequate weight for surgical separation at a later date.     

Extraosseous bone formation in the renal pelvis

PURPOSE: We evaluated the frequency and features of extraosseous bone formation in the kidneys of patients undergoing percutaneous nephrolithotomy. MATERIALS AND METHODS: Percutaneous nephrolithotomy was performed in 621 patients at our institution between 1997 and 2006. In 21 cases metaplastic bone arising from the urothelium was observed. Clinical, radiographic and histopathological features of this group were studied in detail. RESULTS: Patient age ranged from 7 to 40 years (median 11). Extraosseous bone formation was identified in 7 right (33%) and 14 left (67%) kidneys. In all cases extraosseous bone was identified at the angle of the pelvis and ureter, just proximal to the ureteropelvic junction. The typical radiographic appearance of a radiopaque eccentric halo surrounding an area of lesser radiological density connected with the urothelium was seen in 10 of 13 radiographs (77%). Histopathological evaluation showed well formed trabecular bone with surface osteoblastic activity, areas of intratrabecular adipose bone marrow and hematopoietic cells in 5 cases (24%); woven bone intimately related to trabecular bone with scattered hematopoietic cells in 14 (67%); and entirely woven bone with associated mineral deposits and prominent fibroblastic proliferation in 2 (10%). CONCLUSIONS: Although rarely reported in the literature, metaplastic bone formation in the renal pelvis was seen relatively frequently in our patient population. The pathogenesis of this phenomenon is not clearly understood. Recognition of extraosseous bone is important, since it has implications for management and prognosis. In-depth studies of this phenomenon are required to arrive at any conclusions regarding its etiology.