Cattle cooperatives in developing countries.
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Biomedical subjects
Publications and source records attributed to T Gabriel.
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The concept of a pharmacy-coordinated investigational drug service (IDS) is proposed as an approach to better control of investigational drugs. The IDS should be considered as set of service functions aimed to ensure that investigational drug studies in the hospital are executed in a safe, effective, and efficient manner. These functions are the distribution and control of study drugs, clinical services, research activities, and management of clinical studies. The IDS will vary from hospital to hospital, and should reflect the extent to which the institution is involved with research, available resources, and the needs of the hospital. Successful development and operation of an IDS depend on proper planning and continued effective management. The IDS will require resources of personnel, money, and facilities, space, and equipment. The primary expense of the IDS (probably about 80%) will be personnel. Job descriptions for each staff position should be prepared, and a complete set of standard operating policies and procedures is required. Periodic reports summarizing the activities of the IDS and an ongoing quality assurance program are needed. To create an IDS, the pharmacy must acquire the necessary approvals, authority, and resources. The IDS will benefit patients, nursing staff, clinical investigators, hospital risk management, and sponsors of clinical research. These benefits can be used to gain support for the IDS concept. Once the IDS is established, the best promotion will be a successful track of accomplishing the IDS objectives.
A synthetic DNA fragment of 19 residues was enlarged by the enzymatic addition of deoxyadenylate residues to its 3'-end with calf thymus terminal deoxynucleotidyl transferase. The 3'-terminus of this elongated DNA strand was blocked with 2', 3'-dideoxyadenylate to prevent hydrolysis by the 3'-exonuclease function of E. coli DNA polymerase I. This elongated and 3'-blocked fragment was annealed to an oligomeric primer and used as a template for the synthesis of a complementary copy of the synthetic 19-mer. The product of such a repair synthesis was separated by gel filtration and analyzed by nearest neighbor techniques. All template strands were copied with complete repair in over 90% of the chains. Facile recovery of the elongated template by virtue of its size permitted repetition of the copy process, thus allowing accumulation of the desired strand.
Allopurinol (4-hydroxypyrazolo[3,4-d]pyrimidine) has been shown to inhibit the growth of Leishmania braziliensis in vitro at concentrations which are attainable in human tissues and body fluids. This compound is believed to act by interdicting the de novo synthesis of pyrimidines, probably through the formation of allopurinol ribotide. Its lack of toxicity makes it a potential candidate for animal experimentation and it may serve as a prototype for other agents with similar mechanisms of action.
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Analogs of cholecystokinin (CCK-7) in which the N-terminal Tyr(SO3H) was acetylated, Asp6 replaced with Thr(SO3H) and Phe7 replaced with N-methyl-Phe were prepared by solid-phase peptide synthesis and evaluated for their receptor-binding activity and ability to suppress appetite. The receptor binding activities of these synthetic analogs of CCK-7 and their selectivity for the CCK-A and CCK-B receptor subtypes were determined using solubilized membrane preparations from rat pancreatic tissue and bovine striatum. The synthetic peptide Ac-Tyr(SO3H)-Met-Gly-Trp-Met-Thr(SO3H)-N-methyl-Phe-NH2 (referred to as Ro 23-7014) demonstrated superior satiating potency (ED50 = 0.3 micrograms/kg, i.p.), increased selectivity for CCK-A receptors (400-fold), increased resistance to peptidergic degradation and a longer duration of action (4 to 5 hours). This analog also effectively suppressed food intake following intranasal administration (ED50 = 100 micrograms/kg). These studies demonstrate the feasibility of designing analogs of CCK-8 with greater selectivity, potency and duration of action, which may be useful as nonsystemically administered appetite suppressants.