Targeting the dopamine receptor in schizophrenia: investigational drugs in Phase III trials

Introduction: Antipsychotic drugs date back to the 1950s and chlorpromazine. Soon after, it was established that blockade of dopamine and, in particular, the D-2 receptor was central to this effect. Dopamine continues to represent a critical line of investigation, although much of the work now focuses on its potential in other symptom domains. Areas covered: A search was carried out for investigational drugs using the key words `dopamine', `schizophrenia' and `Phase III' in an American clinical trial registry (clinicaltrials.gov), published articles using the National Library of Medicine's PubMed database, and supplemented results with a manual search of cross-references and conference abstracts. Drugs were excluded that were already FDA approved. Expert opinion: There remains interest, albeit diminished, in developing better antipsychotic compounds. The greatest enthusiasm currently centres on dopamine's role in negative and cognitive symptom domains. With theories conceptualising hypodopaminergic activity as underlying these deficits, considerable effort is focused on drug strategies that will enhance dopamine activity. Finally, a small body of research is investigating dopaminergic compounds vis-a-vis side-effect treatments. In domains beyond psychosis, however, dopamine arguably is not seen as so central, reflected in considerable research following other lines of investigation.

DNA binders in clinical trials and chemotherapy

Cancer has always been a dreadful disease and continues to attract extensive research investigations. Various targets have been identified to restrain cancer. Among these DNA happens to be the most explored one. A wide variety of small molecules, often referred to as `ligands', has been synthesized to target numerous structural features of DNA. The sole purpose of such molecular design has been to interfere with the transcriptional machinery in order to drive the cancer cell toward apoptosis. The mode of action of the DNA targeting ligands focuses either on the sequence-specificity by groove binding and strand cleavage, or by identifying the morphologically distinct higher order structures like that of the G-quadruplex DNA. However, in spite of the extensive research, only a tiny fraction of the molecules have been able to reach clinical trials and only a handful are used in chemotherapy. This review attempts to record the journey of the DNA binding small molecules from its inception to cancer therapy via various modifications at the molecular level. Nevertheless, factors like limited bioavailability, severe toxicities, unfavorable pharmacokinetics etc. still prove to be the major impediments in the field which warrant considerable scope for further research investigations. (C) 2014 Published by Elsevier Ltd.

Understanding Medical Device Patenting and Clinical Trials for Product Leadership

Unmet clinical needs remain the primary driving force for innovations in medical devices. While appropriate mechanisms to protect these innovative outcomes are essential, the performance of clinical trials to ensure safety is also mandated before the invention is ready for public use. Literature explaining the relationship between patenting activities and clinical trials of medical devices is scarce. Linking patent ownership to clinical trials may imply product leadership and value chain control. In this paper, we use patent data from Indian Patent Office (IPO), PCT, and data from Clinical Trials Registry of India (CTRI) to identify whether patent assignees have any role in leading as primary sponsors of clinical trials. A total of 42 primary sponsors are identified from the CTRI database in India. Number of patents awarded to these primary sponsors in the particular medical device, total number of patents awarded to the primary sponsor in all technologies, total number of patents in the specific medical device technology provides an indication of leadership and control in the value chain.

Review paper on the production trials of rice-cum fish culture - a transferable concept into Niger State, Nigeria

This paper reviews the production trials of rice-cum-fish culture. Rice and various fish species using rotation and concurrent methods of cultivation are used. The farming system is mostly practiced and researched in to in Southeast Asian countries. It addresses the problems of high external inputs, sustainable aquaculture, poverty and nutrition in the rural population, insect pests, use of insecticides, weeds control and under-utilization of agricultural lands. The production trials yields are summarized and a summary of annual income per hectare from rice and fish have been given. The yield however depends to a large extent on the species stocked, culture period, fertility of the soil and water, degree of supplemental feeding and culturing methods. The production results are discussed. Niger state is blessed with abundant wetlands/rice fields suitable for the practice. However, ecological differences from country to country and region to region, research and development trials are necessary to ensure a successful adoption of the technology to farmers in the State

Analysis of permanent magnets as elasmobranch bycatch reduction devices in hook-and-line and longline trials

Previous studies indicate that elasmobranch fishes (sharks, skates and rays) detect the Earth’s geomagnetic field by indirect magnetoreception through electromagnetic induction, using their ampullae of Lorenzini. Applying this concept, we evaluated the capture of elasmobranchs in the presence of permanent magnets in hook-and-line and inshore longline fishing experiments. Hooks with neodymium-iron-boron magnets significantly reduced the capture of elasmobranchs overall in comparison with control and procedural control hooks in the hook-and-line experiment. Catches of Atlantic sharpnose shark (Rhizoprionodon terraenovae) and smooth dogfish (Mustelus canis) were signif icantly reduced with magnetic hook-and-line treatments, whereas catches of spiny dogfish (Squalus acanthias) and clearnose skate (Raja eglanteria) were not. Longline hooks with barium-ferrite magnets significantly reduced total elasmobranch capture when compared with control hooks. In the longline study, capture of blacktip sharks (Carcharhinus limbatus) and southern stingrays (Dasyatis americana) was reduced on magnetic hooks, whereas capture of sandbar shark (Carcharhinus plumbeus) was not affected. Teleosts, such as red drum (Sciaenops ocellatus), Atlantic croaker (Micropogonias undulatus), oyster toadfish (Opsanus tau), black sea bass (Centropristis striata), and the bluefish (Pomatomas saltatrix), showed no hook preference in either hook-and-line or longline studies. These results indicate that permanent magnets, although eliciting species-specific capture trends, warrant further investigation in commercial longline and recreational fisheries, where bycatch mortality is a leading contributor to declines in elasmobranch populations.

Integrating fish into seasonally flooded rice fields: on-farm trials in Assam, India

In the State of Assam, floodplains cover 2.6 million ha of area that is traditionally rice growing. The ecosystem in the rice-growing areas has undergone major changes as a result of various developmental activities and adoption of modern farming technology. Rice fields were once the major source of fish for the rural farmers. There has been a sharp decline in fish population in rice field leading to a chronic shortage of fish in the State and a deterioration of the rice ecosystem. This paper describes two on-farm experiments for integrating rice cultivation and fish production with the intent of contributing to the understanding of how raising fish can improve rice yields, riceecosystems and farm incomes.

Freshwater prawn farming trials in Bangladesh

Details are given of pond trials conducted in Bangladesh regarding the culture of freshwater prawn (Macrobrachium rosenbergii ). Integrated rice and prawn farming systems were also experimented and results indicated that the prawn could be a suitable species for such integration. Such systems, pond or integrated, are suggested to be best practiced in the southeastern and southwestern areas of the country where there is tidal water exchange and post-larvae are naturally available.

On-farm trials with rice fish cultivation in the west Kano rice irrigation scheme, Kenya

The viability of integrating rice farming with fish culture was studied in ten (10) rice plots. The on-farm research was done during one rice-growing season starting May 2003. The rice variety used was IR 2793-80-1 while the fish species was the Nile tilapia, Oreochromis niloticus. The fish culture period lasted 77 days. An average fish production of 132.4 kg/ha was obtained. The mean recovery rate of tilapia was 43 per cent. Total rice yield from the fields stocked with fish was lower than from unstocked fields. The net returns were not significantly different.

Feeding trials of green seaweed Ulva fasciata

For the nutritional evaluation of green seaweed Ulva fasciata, a feeding trial was performed in albino rats. The results indicated that the 20% replacement of seaweed U. fasciata instead of carrot or lettuce in rad diet causes no harmful effects, as evident by a non-significant change in blood constituents and serum enzyme levels. The weight gain observed in rats with U. fasciata diet was same as that of control diet. The true digestibility ratio of U. fasciata was 80.20% with carrot and 83.4% with lettuce. The data suggest that the green seaweed U. fasciata could be used as an alternative dietary component in animal fodder.

Preliminary trials on the toxicity of "Algistat" to fish and algae

Preliminary toxicity trials conducted with "Algistat" (an algicide) indicated that a dose of 0,66ppm of the compound was highly toxic to fish and 0.8ppm was the general lethal level for Spirogyra sp. The blue green algae, Oscillatoria sp., Mycrocystis sp. and Anabaena sp. were adversely affected by dosages higher than 0.5 ppm Euglena sp. was not affected even at 1.0 ppm.

Field trials on culture of Clarias batrachus

Culture of Magur, Clarias batrachus on an experimental basis was carried out for a total of 159 days in 6 earthen ponds each of 0.02 ha in area, singly in 2 ponds and in combination with Rohu, Labeo rohita in 4 ponds. Three different artificial feeds were used. Growth of Magur varied from 89 to 110 and survival form 93 to 100%. Out of the 3 feeds used, feed formulation 2 yielded better results. Length-weight relationship parameters were found as log W=0.4979067+1.878346 log L; -1.1116438+2.3511497 log L; and -1.238157+2.433125 log L indicating growth to be not isometric. Relative condition factor (K u) was close to or higher than 1.0 only in fishes higher than 200 mm of total length; K. values which were less than 1.0 up to January, reached values greater than 1.0 by March-April. Condition appears to be influenced by spawning rather than feeding.