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Biomedical subjects

C Farmer

Publications and source records attributed to C Farmer.

At least 55 records · Page 3Linked to original sources

Validation of a culture system for porcine pituitary cells: effects of growth hormone-releasing factor and(or) somatostatin on growth hormone secretion.

The goal of the study was to establish the age-related responses of cultured porcine pituitary cells to growth hormone-releasing factor (GRF) and(or) somatostatin (SRIF). A culture system for dispersed porcine pituitary cells was validated. Pituitaries from female pigs of various ages (90 or 110 d of gestation, newborn, 3, 6, or 24 mo old) were enzymatically dispersed with collagenase and neuraminidase, plated (200,000 cells/well), and cultured for 3 d. Plated cells were then subjected to a 4-h challenge with increasing concentrations of GRF (10(-11) to 10(-8) M), SRIF (10(-9) to 10(-6) M), or 10(-8) M of each peptide with increasing concentrations of the other. Culture media were collected and assayed for growth hormone (GH). Pituitaries were pooled so that there were four replicates per age, and treatments were assigned to quadruplicate wells. Concentrations of GH in control wells (basal GH) were maximal at 110 d of gestation and decreased thereafter (P < .01) with increasing age of swine. All peptide combinations affected the GH response (P < .05) at all ages studied, yet GRF was more potent than SRIF in eliciting a response. Age had an effect (P < .05) on the GH response to any of the treatments; younger pigs (90, 110 d of gestation and newborns) had a greater response (P < .05) than older pigs (3, 6, and 24 mo), whereas 6- and 24-mo-old pigs responded similarly in all cases (P > .1).(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Photo-bleaching and photon saturation in flow cytometry.

In flow cytometry, small particles travel at a high speed through a bright light spot. The high light intensity at the point of measurement causes measurable photon saturation. This observation indicates that the rate at which individual dye molecules emit photons is close to the maximum emission rate. Despite the short exposure time, individual molecules may go through a few hundred excitation cycles while they are in the light beam. The absorbed light dose causes significant dye destruction. This article presents experimental procedures to determine the extent of photon saturation and photo-bleaching of dyes bound to cell nuclei in a flow cytometer. Measurements of Hoechst and propidium iodide bound to chromatin show that the amount of dye bleached per emitted photon is the same at low and high illumination intensities. This finding indicates that photon emission and dye destruction are both the result of the absorption of single excitation photons. The experimental observations allow rough estimates of the lifetime of the excited state and the lifetime of the molecule. The lifetime of the Hoechst 33258 bound to DNA is estimated to be 100 excitation-relaxation cycles. The average propidium iodide molecule lasts approximately 200 excitation-relaxation cycles. The theoretical considerations show that the optimal illumination conditions are different for bleaching and nonbleaching dyes. An optical arrangement for high precision measurements of bleaching dyes is presented.

Animals↗

Effect of age and intake on growth hormone kinetics in dairy heifers.

The effects of aging and intake on growth hormone (GH) kinetics and GH-releasing factor (GRF)-induced GH concentrations were studied in two groups of 12 Holstein heifers each (80 d, 85 kg: young; and 273 d of age, 246 kg: old). Each group was then equally subdivided into full-fed (FF) and restricted-fed (RF) subgroups. After 11 d of intake treatment, animals were infused for 3 hr with GH (1.5 mg/hr) in order to calculate GH metabolic clearance rate (MCR), secretion rate (SR) and half-life (t 1/2). Two d later, total plasma volume was determined and the following day, all heifers received a GRF challenge (5 micrograms/kg i.v.). The following values are LSM +/- SE for young-FF, young-RF, old-FF and old-RF. Rate of secretion was not affected by any treatment, averaging 1.51, 1.25, 1.34, and 1.40 +/- .23 micrograms/min. Aging increased (P < .01) MCR (186, 159, 382, and 300 +/- 21 ml/min) and increased plasma volume (P < .01), which resulted in lower basal GH concentrations. Aging also decreased (P < .01) the area under the GH response curve following GRF injection (AUC: 12442, 21114, 5155, and 6308 +/- 1776 ng.min/ml) but did not affect average GH quantity in the plasma after the GRF challenge. Feed restriction decreased (P < .05) MCR, but not enough to affect basal GH concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Carcass composition and resistance to fasting in neonatal piglets born of sows immunized against somatostatin and/or receiving growth hormone-releasing factor injections during gestation.

Thirty-eight gestating sows were either immunized against somatostatin (SRIF) and/or injected with growth hormone-releasing factor (GRF). Treatment effects on carcass composition and resistance of newborn piglets to a 60-hour fast were investigated. Protein content of carcasses at birth was increased in piglets of sows receiving GRF or immunized against SRIF, however, when sows received both treatments there was a reduction in carcass protein content (p = 0.01). Other carcass components were unaltered by treatments, and none of the treatments affected metabolic or endocrine profiles of piglets at birth. Concentrations of GH, IGF-I (p less than 0.01), glucagon and cortisol (p less than 0.05) increased linearly with duration of fast, whereas glucose values decreased. Resistance to fasting was unaltered in piglets from any treatment thereby suggesting that exogenous GRF and/or SRIF immunization of sows during gestation are unlikely to improve survival of newborn piglets.

Animals↗

Lactation performance of sows injected with growth hormone-releasing factor during gestation and(or) lactation.

Fifty-two Yorkshire x Landrace gilts were equally allotted to four treatments: 1) controls, saline injections (CTL); 2) injections of 12 mg of growth hormone-releasing factor (GRF) (1-29)NH2 thrice daily (0700, 1500, and 2300) from d 100 of gestation until parturition (GEST); 3) injections of GRF thrice daily from d 3 to 29 of lactation (LACT); and 4) injections of GRF thrice daily during gestation (d 100 to parturition) and lactation (d 3 to 29) (GEST-LACT). Within 48 h of birth, litters were standardized to 9 +/- 1 pigs. Weights of the pigs were recorded weekly from birth (less than 24 h) until weaning (d 30) and on d 42 and 56. Weights of gilts at mating, d 110 of gestation, 1 d postfarrowing, and at weaning also were recorded. On d 24 of lactation, milk yield was estimated by the weigh-suckle-weigh method, and a representative milk sample was obtained the next day. Jugular vein cannulas were inserted into six sows per treatment on d 26, and a 6-h blood profile (sampling every 20 min from 0600 to 1200) was obtained on d 29. Daily feed consumption of sows was recorded throughout the study. Weights of the pigs at any one time or survival until weaning were not affected by treatments (P greater than .1). Sows injected with GRF during GEST (P = .05) and(or) LACT (P less than .01) were lighter than CTL sows at weaning; in addition, sows treated during lactation had less backfat (P less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

In vivo growth hormone (GH) response to human GH-releasing factor (GRF) or somatostatin (SRIF) in foetal pigs.

The short-term effect of hypothalamic GRF and SRIF on the pituitary release of GH at different stages of gestation has been studied. In the present experiment eighteen gilts were used, six at each of 66, 88 and 110 days of gestation. Ventral laparotomy was performed under general anaesthesia and a section of uterus was exteriorized. Blood samples were obtained from the umbilical vein of three foetuses per gilt just prior to the injection of each foetus with either saline, 5 micrograms/kg of hGRF (1-44)NH2 or 50 micrograms/kg of SRIF into the umbilical vein. Additional blood samples were obtained 15, 30, 45 and 60 min post-injection. Serum samples were radioimmuno-assayed for GH (porcine). There was a treatment by gestational age interaction (P less than 0.01) on mean GH concentrations, area under the GH curve and GH peaks. While treatments had no effect (P greater than 0.1) on GH variables at 66 days of gestation, the area under the GH curve was slightly increased by GRF (P = 0.14) at day 88 and all GH variables were significantly increased (P less than 0.01)) by GRF at 110 days of gestation. There was a quadratic effect of time post-injection on GH concentrations at 88 (P less than 0.05) and 110 (P less than 0.001) days of gestation. There was no effect of SRIF injection (P greater than 0.1) on GH concentrations at any gestational age. In conclusion, the foetal pituitary responsiveness to GRF develops with foetal age and is maximal at the end of gestation, whereas there is no short-term response to a bolus of SRIF at any stage of gestation.

Animals↗

Pirmenol: an antiarrhythmic drug with unique electrocardiographic features--a double-blind placebo-controlled comparison with quinidine.

Previous reports have stated that pirmenol is a Class IA antiarrhythmic drug that prolongs the QT interval, but did not use computerized electrocardiography. We randomized 18 patients with frequent ventricular ectopic depolarizations to pirmenol (8 patients) or quinidine (10 patients). Pirmenol was effective and tolerated for suppression of arrhythmia in all 7 patients treated (1 patient withdrew for personal reasons) but quinidine was effective and tolerated for 4 weeks in only 5 of 10 patients (p less than 0.05). Using computerized 12-lead electrocardiography, the mean change in PR interval from placebo to treatment was 5 +/- 18 ms for quinidine and 5 +/- 11 ms for pirmenol (p = NS). The mean change in QRS interval was 5 +/- 14 ms for quinidine and 10 +/- 5 ms for pirmenol (p = NS). The mean change in QT interval was 46 +/- 30 ms for quinidine and 8 +/- 9 ms for pirmenol (p less than 0.01) and the mean change in JT interval was 41 +/- 36 ms for quinidine and -2 +/- 10 ms for pirmenol (p less than 0.01). After the double-blind phase, 4 quinidine patients had computerized electrocardiographic intervals measured on pirmenol; the above findings were confirmed. These electrocardiographic features of pirmenol clearly distinguish it from quinidine, the prototype Class IA drug. However, pirmenol has minimal effect on the PR and QRS intervals, and thus does not appear to be a Class IC drug either. Although its electrocardiographic features are closest to Class IB, its electrophysiology in isolated cells and its antiarrhythmic and side effect profile are atypical for a IB agent.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Arrhythmia Agents↗

Effects of active immunization against somatostatin (SRIF) and/or injections of growth hormone-releasing factor (GRF) during gestation on hormonal and metabolic profiles in sows.

The hormonal responses of gestating sows to immunization against somatostatin conjugated to bovine serum albumin (SRIF-IMM) and/or injections of growth hormone-releasing factor (GRF) were studied with thirty-eight second parity sows. Immunization against bovine serum albumin (BSA-IMM) was used as control. First immunizations were done on day 30 and boosters were given on days 44, 58, 72, 86 and 100 of gestation. Injections of GRF (9 mg of GRF (1-29)NH2 per injection) or saline were given at 0800, 1400 and 2000 hr daily from day 90 of gestation until parturition. Mean body weights of sows at 85 and 110 d of gestation were 196.3 and 210.5 kg, respectively (SE = 0.8). Jugular blood samples were collected from 0740 hr to 1100 hr at 20 min intervals on days 90, 101 and 112 of gestation. On day 112, additional samples were collected from 1340 hr to 1700 hr and from 2140 hr to 2300 hr. At 112 d of gestation, antibody titers against SRIF (% binding, 1:150 dilution) were higher (P less than 0.01) for SRIF-IMM (13.5%) vs BSA-IMM (0.95%) sows. There was no effect of SRIF-IMM nor was there a GRF by SRIF-IMM interaction on any variable measured (P greater than 0.05). Injections of GRF increased (P less than 0.01) the area under the curve (AUC) for growth hormone (GH; 305 vs 1623 ng/min/ml). The increase was greater as days of injection increased (P less than 0.05). Administration of GRF did not affect prolactin (Prl) AUC (P greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Hormonal changes following an acute stress in control and somatostatin-immunized pigs.

Sixteen Yorkshire pigs (49 +/- 2 kg BW at 17 weeks) were immunized against somatostatin (SRIF; 4 males, 4 females) or its conjugated protein, bovine serum albumin (BSA; controls; 4 males, 4 females). Immunizations were done at 10, 12 and 14 weeks of age. Jugular vein cannulae were surgically inserted at 17 weeks of age. Five d later, half of each sex from the control and SRIF-immunized groups were stressed. The other half were subjected to the same stress 48 hr later. On both days, remaining animals were used as unstressed controls. The stress consisted of 5 min of snare restraint. Blood samples were collected from all pigs on both days at -20, -15, -10, -5, 0 (beginning of stress), 2, 6, 10, 15, 20, 30, 40, 60, 90, 120, 150, 180 and 240 min. Samples were radioimmunoassayed for cortisol, growth hormone (GH), prolactin (Prl), insulin, triiodothyronine (T3), thyroxine (T4) and insulin-like growth factor I (IGF-I). Mean antibody titers against SRIF (1:150 dilution) at 15 weeks were 0.49 +/- .09% and 54.5 +/- 4.9% for control and SRIF immunized pigs, respectively. Gender and immunization against SRIF had no effect on any of the variables measured (P greater than 0.05), except for T3 levels which were greater in females than in males (P less than 0.05). The stress by time of sampling interaction was significant (P less than 0.01) for all hormones measured. Cortisol values almost tripled within 15 min of stress, reaching concentrations above 100 ng/mL. Maximal increases were seen at 2 min for T4 (14%), at 6 min for T3 (36%), at 15 min for Prl (46%) and at 10 min for insulin (141%). An increase of 129% in GH concentration was present at 20 min in stressed pigs; however, an increase of 97% was also seen at 120 min in control pigs. Concentrations of IGF-I decreased (21%) by 60 min in the stressed pigs and remained depressed for up to 150 min. Stress associated with snare restraint, therefore, induces major changes in the concentrations of a series of hormones in growing pigs. On the other hand, immunization against SRIF did not alter any of the hormonal profiles measured. Since snare restraint is widely used to handle pigs during jugular puncture, any study of hormonal secretion in this species should be carried out under carefully controlled conditions in terms of blood sampling technique.

Animals↗

Strength training does not improve lipoprotein-lipid profiles in men at risk for CHD.

Sixteen untrained males, age 46 +/- 11 yr (mean +/- SD), were studied to determine the effects of 20 wk of strength training on lipoprotein-lipid profiles and post-heparin lipase activities. All subjects had abnormal lipoprotein-lipid profiles and at least two other risk factors for coronary heart disease (CHD). To control for day-to-day variations in blood lipoprotein levels, baseline values were established by taking at least two blood samples on separate days from the training and control groups. The training program resulted in a 50% increase in upper body strength (P less than 0.001) and a 37% increase in lower body strength (P less than 0.001) as measured by the one repetition maximum test (1-RM). No changes in the 1-RM test were observed in the control group. There were no significant changes in VO2max (34.5 +/- 6.4 vs 36.2 +/- 7.4 ml.kg-1.min-1 or percent fat (25.4 +/- 4.2 vs 24.9 +/- 4.1%) with training. There were also no significant changes in plasma concentrations of triglyceride (193 +/- 96 vs 171 +/- 101 mg.dl-1), total cholesterol (231 +/- 22 vs 210 +/- 22 mg.dl-1), and HDL-C (35 +/- 6 vs 36 +/- 8 mg.dl-1), or LDL-C (139 +/- 16 vs 139 +/- 21 mg.dl-1). Furthermore, the activities of post-heparin lipoprotein lipase (9 +/- 4 vs 13 +/- 5 moles.ml-1.h-1) and hepatic lipase (35 +/- 10 vs 35 +/- 9 moles.ml-1.h-1) did not change with training.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effect of dose and frequency of administration of a potent analog of human growth hormone-releasing factor on hormone secretion and growth in pigs.

Ninety-six pigs (49.5 +/- .5 kg BW) were allotted to six treatments and were injected once (SID) or three times daily (TID) s.c. with a [desamino-Tyr1, D-Ala2, Ala15] human growth hormone-releasing factor (1-29) NH2 analog (GRF-AN). Treatments were T1, noninjected control; T2, saline-injected control (TID); T3, GRF-AN (1.66 micrograms/kg BW, TID); T4, GRF-AN (3.33 micrograms/kg BW, TID); T5, GRF-AN (6.66 micrograms/kg BW, TID) and T6, GRF-AN (10 micrograms/kg BW, SID). Feed protein levels were 14% for T1 and 18.8% for T2 through T6. The GRF-AN increased serum growth hormone (GH) concentration for the entire growing period (about 56 d) in a dose-related manner and did not induce desensitization of the somatotroph cells; in fact, an increase (P less than .05) in the GH response to GRF-AN was observed in T4 and T5 after 1 mo of treatment. This GRF-AN produced (P less than .05) a dose-dependent effect on several variables in animals grown to 110 kg BW: in comparison to T2, T5 increased meat in carcass (6%), carcass length (3%), loin eye area (13%), liver weight (19%), kidney weight (30%), improved feed efficiency (20%) and decreased total feed intake by 50 kg (26%). Compared to T2, average daily gain was increased (P less than .05) by 13% by the 3.33 micrograms/kg TID dose. Blood parameters were measured on d 1, 29 and 57. Increased serum glucose and insulin levels were observed. Triiodothyronine and thyroxine concentrations were increased and decreased, respectively after 28 d of treatment but were unchanged on d 57. This potent GRF analog maintained high GH concentration for at least 56 d and affected several growth parameters and carcass characteristics in a dose-related manner similar in magnitude to that reported in studies using porcine GH.

Animals↗

Heat loss in exposed volunteers.

Hypothermia is a common complication of major surgery and trauma. We studied this problem using Heat Flux Transducers to directly measure heat exchange between seven exposed volunteers and the environment. Heat exchange by radiation and convection was measured from the anterior chest wall and by conduction, between the back and a thermal mattress (CSZ, Blanketrol II). We determined the coefficients for: radiation = 6.6; convection = 8.3 square root of v; combined radiation and convection = 9.7; conductance = 41, all expressed in W/m2.degrees C. The clinical significance of these results is that heat loss, by radiation and convection alone, is 10 W/m2.degrees C. However, heat production under anaesthesia is only 40 W/m2, so a temperature gradient of greater than 4 degrees C between the skin and environment will cause more heat to be lost than is produced. The thermal mattress can supply 41 W/m2.degrees C, effectively doubling heat production.

Body Temperature Regulation↗

Design and trial of a metronidazole loading dose regimen for patients undergoing emergency surgery.

A dosing regimen for administration of metronidazole to patients undergoing emergency surgery was designed using pharmacokinetic data. Computer estimates of the pharmacokinetic parameters from normal volunteers were used to determine a loading dose protocol that would achieve plasma metronidazole levels above 6.2 micrograms/mL, that is, above the minimum inhibitory concentration (MIC) of most pathogenic anaerobic bacteria, at the time of surgery. The protocol aimed to identify the minimum intravenous metronidazole dose in combination with a rectal suppository regimen. This was calculated to be a 1 g (two 500 mg) metronidazole rectal suppository dose administered when the decision to operate was made, followed by a 200 mg intravenous dose at the induction of anaesthesia if the time to surgery was within 1-8 h. This protocol was tested in 10 patients undergoing emergency abdominal/pelvic surgery. All patients in the trial were found to have levels well above the MIC at the time of surgery (mean = 17.06 micrograms/mL, s.d. = 4.76). It is concluded that appropriate use of metronidazole suppositories can minimize intravenous dosage requirements for metronidazole under conditions of emergency loading as well as elective surgery.

Abdomen↗

Estrone concentration in sow milk during and after parturition.

Colostrum and milk samples were obtained from five Yorkshire gilts through manual expression of glands at the onset of parturition; at 1, 2, 4 and 8 h after birth of the first piglet and at 8-h intervals thereafter until 96 h. Oxytocin (30 units) was used to stimulate milk ejection for all samples except during parturition. Samples were frozen until subjected to a validated radioimmunoassay for estrone (E1). In a preliminary study no differences existed in concentrations of E1 among various glands. Therefore, mean of values obtained from three randomly selected glands was used for analysis in the main trial. Concentration of E1 at birth averaged 13.6 +/- 1.78 ng/ml (X +/- SE), and decreased to 6.05 +/- .80, 3.12 +/- .60, 1.42 +/- .30, .69 +/- .20 and .33 +/- .92 ng/ml at 4, 8, 16, 32 and 96 h, respectively. The postpartum decrease in the concentration of E1 in the milk is most likely due to the loss of the placental source.

Animals↗

Relationship of estrone and prolactin with growth and survival of piglets to 35 d of age.

The relationship between estrogen or prolactin (Prl) status of pigs at birth and subsequent performance was examined in ten (Study 1) or seven (Study II) Yorkshire litters. In both studies, piglets were bled (3 ml) from the suborbital sinus at birth, and then hourly for 12 h. Hematocrit (Hct) and concentrations of plasma protein (PP) and estrone (E1) were determined on all samples. Concentrations of Prl were determined only in samples at birth. Weights at 3 and 5 wk of age as well as percent survival to 5 wk were obtained. Mean concentrations of E1 and Prl in piglets at birth were 6.97 +/- 44 ng/ml and 9.12 +/- .32 ng/ml, respectively. A decrease in E1 occurred over the first few hours after birth. Hematocrit values also decreased postnatally, whereas concentrations of PP increased. Sex of neonate did not affect any of the blood characteristics studied. Correlations between E1, PP, Hct and Prl at birth and body weights at birth, 3 and 5 wk were nonsignificant. However, piglets with higher Prl values at birth showed a greater survival rate. In Study II, half of the piglets in each litter were implanted at birth with silicone rubber implants containing estradiol-17 beta. Estrone concentrations were significantly higher in implanted piglets than in controls over the subsequent 12-h period, but Hct and PP values were not affected by treatment, suggesting that treated piglets did not consume more colostrum.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗