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Biomedical subjects

J R Weeks

Publications and source records attributed to J R Weeks.

18 recordsLinked to original sources
PubMed1991

Infant mortality among ethnic immigrant groups.

The numerically large and growing Indochinese refugee population has been little studied with respect to infant health. It is a population that is young, is experiencing high fertility, late onset of prenatal care, and is characterized by low socioeconomic status. Thus, it presents a high risk profile with respect to infant mortality. Using linked birth and infant death records for the San Diego metropolitan area for the period 1978-85 infant mortality rates (IMRs) were calculated for Indochinese refugee groups from Vietnam, Laos and Cambodia in comparison with other ethnic groups. We found, surprisingly, that Indochinese refugees as a group had an IMR below that for non-Hispanic Whites and substantially below that for Blacks. In general, IMRs for Indochinese refugees were similar to those for other Asian groups. These findings held even after controlling for birth weight and onset of prenatal care. The timing and causes of death suggest areas in which the IMR could drop to even lower levels with improved community outreach programs, especially among refugee groups from Laos (Hmong and Lao) who exhibited the unusual pattern of higher post-early neonatal than early neonatal mortality.

Birth Weight↗
PubMed1979

Prostaglandin prodrugs. I: Stabilization of dinoprostone (prostaglandin E2) in solid state through formation of crystalline C1-phenyl esters.

Dinoprostone para-substituted phenyl esters were synthesized in attempt to improve the solid-state stability of the parent prostaglandin. A phenol series covering a wide melting-point range was employed, and a linear relationship was observed between the phenol melting points and the resulting prostaglandin C1-ester melting points. The crystalline esters showed improved solid-state stability over the parent compound, and many esters were biologically active.

Animals↗
PubMed1979

Prostaglandin prodrugs III: Synthesis and biological properties of C9- and C15-monoesters of dinoprost (prostaglandin F2 alpha).

Methods are described for the synthesis of dinoprost C9- and C15-monoesters using protective groups. Esters at C9 were synthesized by acylation of dinoprost 11,15-bis(tetrahydropyran-2-yl)ether followed by acid-catalyzed protective group removal. Esters at C15 were synthesized by initial formation of the protected intermediate, dinoprost 9,11-n-butylboronate, followed by acylation and hydrolytic protective group removal. Many esters were active in vivo in the hamster antifertility screen. Plasma hydrolysis studies showed that the C15-esters were more readily cleaved than the C9-esters. In vivo studies in the rat showed that both the C9- and C15-esters resulted in urinary excretion of 5 alpha, 7 alpha-dihydroxy-11-ketotetranorprosta-1,16-dioic acid in amounts comparable to those obtained after dosing with dinoprost, indicating that ester hydrolysis occurred in vivo.

Animals↗
PubMed1979

Dose and physical dependence as factors in the self-administration of morphine by rats.

Groups of naive rats were offered morphine sulfate for self-admininstration in doses of 0.0032-10 mg/kg for 6 days. On day 7 saline was substituted for morphine. Loss of weight was taken as physiological evidence of dependence. Rats that did not lose weight formed a single population whose mean injection rate did not differ from control rats receiving only saline injections. Injection rates for rats losing weight were log-normally distributed, and the mean of the logarithms of the injection rates was linearly related to the logarithm of the dose. Mean daily injection rates averaged 12 for controls, 23 at 10 mg/kg, and 411 at 0.01 mg/kg. A transient increase in morphine intake after an injection of nalorphine was taken as behavioral evidence of dependence. Nalorphine increased morphine intake when rats were self-injecting 0.32 and 1.0 mg/kg of morphine, but not 0.032 or 0.1 mg/kg. The reinforcing property of morphine may occur without behavioral evidence of dependence.

Animals↗
PubMed1979

A method for administration of prolonged intravenous infusion of prostacyclin (PGI2) to unanesthetized rats.

Prostacyclin is short acting and chemically unstable. To study sustained effects in an intact animal, prolonged intravenous infusion may be required. The compound has adequate stability for 24 hr in pH 10.0 carbonate buffer at 0 degrees. A "displacement syringe" is described wherein the prostacyclin solution is stored in a rubber bag inside the barrel of a 5 ml syringe. This device is placed in an ice bath. A syringe pump drives water into the barrel displacing an equal volume of solution out of the bag. Chronic venous cannules, saddles, and flow-through swivels are used as for drug self-administration studies. A simple, inexpensive rack for use with conventional individual hanging cages is also described.

Animals↗
PubMed1979

The cardiovascular pharmacology of prostacyclin (PGI2) in the rat.

Physiological roles have been suggested for prostacyclin in the cardiovascular system. Prostacyclin was administered by intravenous infusion to unanesthetized rats. Over a 24 hr period, 0.32 mg/kg/day caused only flushing of the ears. Larger doses (0.56 and 1 mg/kg/day) caused hypothermia, behavioral depression, and swelling of the paws. Cumulative dose-response curves for its depressor action were determined in both unanesthetized and anesthetized, vagotomized, ganglion-blocked rats. In unanesthetized rats, the threshold dose was about 0.1 ug/kg/min. Respiratory depression precluded doses larger than 1 ug/kg/min. In anesthetized rats, the threshold dose was about 0.001 ug/kg/min, and the maximally effective dose was about 0.1 micrograms/kg/min. At 0.032 ug/kg/min, blood pressure first fell and then rose slightly. This compensatory rise did not occur in nephrectomized rats, suggesting renin release as the mechanism. Intravenous infusion of 0.1 but not 0.01 ug/kg/min in unanesthetized rats doubled plasma renin activity. In saline-loaded unanesthetized rats, urine volume and urinary sodium excretion were decreased by 0.1 ug/kg/min of prostacyclin.

Animals↗
PubMed1979

Synthesis and biological properties of 9-deoxo-16,16-dimethyl-9-methylene-PGE2.

The in vivo monkey uterine stimulating potency of 9-deoxy-16,16-dimethyl-9-methylene-PGE2 is similar to that of 16,16-dimethyl-PGE2 and approximately 15 times that of PGE2. Low doses of this compound stimulated uterine contractions when administered vaginally. Pregnancy was terminated prematurely following subcutaneous, intramuscular or vaginal suppository treatment. Estimates of potential for gastrointestinal side effects using the rat enteropooling assay and in vivo monkey effects indicate that diarrhea will be substantially reduced with retention of uterine stimulating potency.

Abortion, Induced↗
PubMed1979

Metabolism of prostacyclin. III. Urinary metabolite profile of 6-keto PGF1 alpha in rat.

The in vivo metabolism of 6-keto PGF1 alpha was investigated in rats. Following continuous intravenous infusion for 14 days the urinary metabolites were isolated and identified. A substantial amount of unchanged 6-keto PGF1 alpha was recovered in the urine. The metabolic pattern very closely resembles that of PGI2 in rats. Metabolites were found which represented 15-dehydrogenation, beta-oxidation, omega and omega-1-hydroxylation and oxidation. Previous work showed that 6-keto PGF1 alpha is very poorly oxidized by 15-PGDH. We administered 15-[H3]-PGI2 and 15-[H3]-6-keto PGF1 alpha to rats and measured urinary tritiated water as an index for in vivo 15-PGDH activity. The results showed that PGI2 and 6-keto PGF1 alpha were both oxidized to the 15-keto product, although the rate of oxidation of PGI2 was greater than that of 6-keto PGF1 alpha. We concluded that the administered PGI2 was oxidized by 15-PGDH before hydrolysis to 6-keto PGF1 alpha. A portion of the dose is probably hydrolzyed before 15-dehydrogenation.

Animals↗
PubMed1978

Self-administration of morphine in the rat: relative influence of fixed ratio and time-out.

Rats were offered 3.2 mg/kg of morphine sulfate on a continuous reinforcement schedule until the daily injection rate had stabilized. The effect of fixed ratio schedules of 4 and 8 were compared to imposing time-out periods of 5 and 10 sec immediately followed each injection. The fixed ratio schedules decreased the injection rate while the time-out schedules had no effect. The hypothesis that the effect of a fixed ratio schedule is a consequence of imposing a time-out period, allowing full effects of the injection to be sensed, is not supported.

Animals↗
PubMed1978

The general pharmacology of prostacyclin PGI2, (PGX): a new prostaglandin especially active on the cardivascular system.

Prostacyclin is a new prostaglandin first demonstrated as a product of arterial microsomes and prostaglandin endoperoxide intermediates. The potential to form prostacyclin has now been demonstrated in many organs. It inhibits platelet aggregation, inhibits gastric acid secretion, stimulates the monkey but not the rat uterus in vivo, is a bronchodilator, is a vasodepressor on both systemic and pulmonary circulation, increases cardiac output and markedly decreases peripheral resistance. It reduced progesterone in pregnant hamsters but is not luteolytic in non-pregnant monkeys. In rats, i. v. infusion of 0.56 but not 1 mg/kg/day was tolerated without overt central nervous system depression. The depressor effect of i. v. infusions of prostacyclin in anesthetized rats was partially antagonized by a pressor reaction eliminated by nephrectomy, an effect not seen during infusions of prostaglandin.

Animals↗
PubMed1977

The pneumatic syringe: a simple apparatus for self-administration of drugs by rats.

Drug solution is delivered by a syringe operated by a pneumatic cylinder. Recommended delivery volumes are from 10 to 200 microliter. A solid-state control unit is described which can operate two syringes (drug injection and flush), has outputs for recording responses and injections, and can be programmed to provide several schedules of reinforcement. All components are readily commercially available.

Animals↗
PubMed1976

Changes in morphine self-administration in rats induced by prostaglandin E1 and naloxone.

Interactions of prostaglandin E1 (PGE1) with morphine have been reported in several test systems and an hypothesis has been advanced for a role of prostaglandins in morphine analgesia and physical dependence. In rats self-administering morphine intravenously, a simultaneous and continuous infusion of naloxone hydrochloride at 56 to 560 mug/kg/day caused the expected increase in injection rate for morphine. Infusion of PGE1 by itself at 56 or 180 mug/kg/day had no effect on the rate of morphine intake. Likewise the addition of PGE1 at 180 mug/kg/day did not potentiate the increase caused by naloxone (56 or 180 mug/kg/day) when it was added to the naloxone infusion. These results do not support a role for prostaglandins in the behavioral aspects of morphine addiction. However, larger doses of PGE1 (1 and 1.8 mg/kg/day), which were without overt effects in normal rats, caused severe and incapacitating prostration in morphinized rats.

Animals↗
PubMed1976

Introduction to cardiovascular research on prostaglandins.

The prostaglandins have diverse cardiovascular effects, differing not only among themselves but also according to the organ affected and the species. Some of the pharmacological actions of the prostaglandins may have practical application in hypertensive crises, shock, peripheral vascular disease, and to maintain the patency of the ductus arteriosus in congenital heart malformations. They may play physiological roles as locally produced modulators or regulators of kidney function and blood flow to specific organs or tissues. Such roles are yet to be firmly established.

Animals↗
PubMed1975

Biological activities of 17-phenyl-18,19,20-trinorprostaglandins.

In a number of assay systems, some 17-phenyl-trinor-prostaglandins were similar in activity and potency to the corresponding parent prostaglandin. In others, the 17-phenyl analogs appeared several times more potent. In the hamster antifertility assay, which is considered to measure luteolytic activity, 17-phenyl-18,19,20-trinor prostaglandin F2alpha was about 90-times PGF2alpha in potency. Rat blood pressure responses to 17-phenyl analogs were significant. The 17-phenyl-trinor PGF2alpha pressor potency was 5 times that of PGF2alpha. The 17-phenyl-trinor PGE2 blood pressure response was atypical since a pressor rebound phenomenon followed the expected depressor response. Lastly, 17-phenyl-trinor PGF2alpha was more potent than PGF2alpha in synchronizing the estrous cycle in beef cows.

Animals↗
PubMed1975

Environmental influences affecting the voluntary intake of drugs: an overview.

Drug self-administration studies in animals have generally used drugs that are abused by man. The oral route by adding drug to the drinking water is simple, but the bitter taste of many drugs requires that the animals first be forced to consume treated water. The intravenous route, wherein relatively unrestrained rats or monkeys press a lever to obtain intravenous drugs, permits precise control over the dose and can be readily adapted to schedules and manipulations customarily used in the behavioral sciences. Environmental factors affecting drug intake include the dose its schedule of administration, and conditioning of drug administration to secondary cues. There are differences in drug self-administration of stimulant drugs (as amphetamines) and depressants (as morphine and barbiturates). There is an inverse relation between the size of the dose and number of injections taken, but for stimulants daily intake will remain constant whereas for depressants smaller doses are only partially compensated for by increased numbers of injections. Likewise, drug intake of stimulants is better maintained on ratio schedules. Neutral stimuli, as lights or buzzers, paired with drug injections can be used to elicit conditioned responses. Such responses have been used to evaluate the reinforcing properties of drugs.

Administration, Oral↗