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Biomedical subjects

H Hobbs

Publications and source records attributed to H Hobbs.

11 recordsLinked to original sources
PubMed2001

Discovery of 4-[3-(trans-3-dimethylaminocyclobutyl)-1H-indol-5-ylmethyl]-(4S)-oxazolidin-2-one (4991W93), a 5HT(1B/1D) receptor partial agonist and a potent inhibitor of electrically induced plasma extravasation.

Utilizing a pharmacophoric model of binding of 3-(2-aminoethyl)indoles to 5HT(1B/1D) receptors, we identified the 3-aminocyclobutyl group as a potential ethylamine isostere. A novel multidimensional chemometric approach was used to predict the intrinsic activity (degree of agonism) at the receptor. A qualitative model for pharmacokinetic properties was then used to guide the synthesis toward molecules likely to have oral bioavailability in humans. A novel synthetic route to 3-(3-dimethylaminocyclobutyl)indoles was developed. Analogues showed generally lower intrinsic activity at 5HT(1B/1D) receptors than their ethylamine counterparts. 4-[3-(trans-3-Dimethylaminocyclobutyl)-1H-indol-5-ylmethyl]-(4S)-oxazolidin-2-one (4991W93, 1) was identified as a partial agonist against 5HT(1B/1D) receptors, with low intrinsic activity. This molecule also has significant activity against 5HT(1F) receptors but is selective over other 5HT receptors. In addition this compound was found to be an exceptionally potent inhibitor of electrically induced plasma extravasation. Compound 1 may have utility in the treatment and prophylaxis of migraine.

Administration, Oral↗
PubMed2001

A reliable method for isolation of viable porcine islet cells.

HYPOTHESIS: Mechanical injury and oxidative stress caused by reoxygenation of isolated porcine islet cells result in their unresponsiveness to glucose stimulation. DESIGN: Adult pigs (weighing 25-30 kg) were anesthetized, and following intra-arterial infusion of ice-cold University of Wisconsin solution, a complete pancreatectomy was performed. The pancreatic duct was cannulated for infusion of digestion medium containing collagenase type P, 1.5 mg/mL; deoxyribonuclease I, 10 000 U; and a water-soluble analogue of vitamin E (Trolox), 1 mmol/L. After 20-minute incubations on ice, and at 37 degrees C, the pancreas was hand shaken for 1 minute, followed by filtration and separation on an automatic cell separator (COBE 2991). Islet cells, identified by dithizone staining, were perifused at 37 degrees C. RESULTS: The mean +/- SEM yield of intact purified islet cells (50-200 microm in diameter), and mostly present in clusters, was 2398 +/- 143 cells per gram (n = 12). Glucose stimulation caused a significant increase in biphasic insulin secretion in the perifusion experiments. CONCLUSION: We have developed a simple, reproducible, and reliable procedure for isolating intact and viable porcine islet cells suitable for xenotransplantation.

Animals↗
PubMed1999

Synthesis and serotonergic activity of substituted 2, N-benzylcarboxamido-5-(2-ethyl-1-dioxoimidazolidinyl)-N, N-dimethyltryptamine derivatives: novel antagonists for the vascular 5-HT(1B)-like receptor.

The synthesis and vascular 5-HT(1B)-like receptor activity of a novel series of substituted 2, N-benzylcarboxamido-5-(2-ethyl-1-dioxoimidazolidinyl)-N, N-dimethyltryptamine derivatives are described. Modifications to the 5-ethylene-linked heterocycle and to substituents on the 2-benzylamide side chain have been explored. Several compounds were identified which exhibited affinity at the vascular 5-HT(1B)-like receptor of pK(B) > 7.0, up to 100-fold selectivity over alpha(1)-adrenoceptor affinity and 5-HT(2A) receptor affinity, and which exhibited a favorable pharmacokinetic profile. N-Benzyl-3-[2-(dimethylamino)ethyl]-5-[2-(4,4-dimethyl-2, 5-dioxo-1-imidazolidinyl)ethyl]-1H-indole-2-carboxamide (23) was identified as a highly potent, silent (as judged by the inability of angiotensin II to unmask 5-HT(1B)-like receptor-mediated agonist activity in the rabbit femoral artery), and competitive vascular 5-HT(1B)-like receptor antagonist with a plasma elimination half-life of approximately 4 h in dog plasma and with good oral bioavailability. The selectivity of compounds from this series for the vascular 5-HT(1B)-like receptors over other receptor subtypes is discussed as well as a proposed mode of binding to the receptor pharmacophore. It has been proposed that the aromatic ring of the 2, N-benzylcarboxamide group can occupy an aromatic binding site rather than the indole ring. The resulting conformation allows an amine-binding site to be occupied by the ethylamine nitrogen and a hydrogen-bonding site to be occupied by one of the hydantoin carbonyls. The electronic nature of the 2,N-benzylcarboxamide aromatic group as well as the size of substituents on this aromatic group is crucial for producing potent and selective antagonists. The structural requirement on the 3-ethylamine side chain incorporating the protonatable nitrogen is achieved by the bulky 2, N-benzylcarboxamide group and its close proximity to the 3-side chain.

Animals↗
PubMed1999

The Alumni program: redefining continuity of care in psychiatry.

The Alumni Program is a novel approach to the continuing care and preventive treatment of clients with "chronic" mental illness. This approach demands a different conceptualization of outpatient psychiatric intervention. The infectious disease model has been deliberately replaced with a chronic illness model that more accurately reflects the course and natural history of psychiatric illness. The Alumni Program is similar to the approach employed with other chronic medical conditions like arthritis, asthma, or diabetes. The program has complementary roles for both specialty psychiatric clinicians and family practitioners. In addition, the program empowers clients and their families to play a key role in their own ongoing adaptation and adjustment to chronic illness while striving for optimal wellness.

Aftercare↗
PubMed1999

The family educator: a professional resource for families.

The family educator works with the client's family members to help in their understanding of their ill relative and to assist with managing the stress of the caregiver role. Families come to understand that they can join forces with the clinical team in helping their relative engage in a trial of treatment. Each treatment recommendation is explained to the family and decisions are arrived at by consensus through partnership meetings. Role modeling effective interaction approaches and providing assistance in generating alternative solutions to problematic situations are important functions of the family educator.

Family↗
PubMed1997

Continuous ambulatory peritoneal dialysis. Experience in a single renal unit in the UK.

The outcome of 106 patients started on continuous ambulatory peritoneal dialysis (CAPD) in a single renal unit over a 3-year period was reviewed in order to compare our experience with that of other centres. The incidence of peritonitis was not different in diabetics compared with non-diabetics, in the elderly compared with younger patients, and in non-compliant compared with compliant patients. The patients' level of education had a significant effect on the number of days required to train for CAPD. Diabetics and non-compliant patients required more hospitalization. The need for community support increased the incidence of peritonitis.

Adult↗
PubMed1995

Therapeutic partnership. A model for clinical practice.

The illness of a relative disturbs family equilibrium and creates a stressor of significant magnitude. Thus, interpretations of individual or family functioning must be placed in this context. The Therapeutic Partnership model is adept at reinforcing shared responsibility, accountability, and decision making. It conveys a culture of hope and appears to achieve its desired goals. Therapeutic Partnership stands in direct contrast to the notion of lifetime advocacy and other more traditional treatment approaches. It is a highly intense, time-limited, goal-directed involvement.

Adult↗