Physiologic effects of a self-contained self-rescuer

Recently promulgated federal regulations mandate the provision of an emergency, self-contained, oxygen-supplying breathing device (self-contained self-rescuer, SCSR) to all underground coalminers. In order to assist in defining the potential limitations of this new device, we measured the responses of ten healthy coal mine inspectors to submaximal steady-state treadmill exercise with and without the SCSR. During the last minute of exercise, blood oxygen saturation averaged 98.3% and mouth pressure swing 15.6 cm H2O with the device, compared to 94.8% and 10.4 cm H2O without it. Mean respiratory rates were decreased to 25/min with the SCSR from 28/min without it. Blood pressure, core temperature and heart rate were unaffected. We conclude that in healthy individuals on submaximal exercise there is little evidence of a significant adverse effect of the new device.     

Physiologic effects of maternal smoking on breast-feeding infants

Women who smoke and breast-feed pose an unknown threat to their infants' health. In this pilot study, relationships between ingestion of nicotine in breast milk and physiologic effects in the infant were investigated. Infant physiologic effects measured were temperature, pulse, respiration, systolic blood pressure, and oxygen saturation. Five smoking and five nonsmoking mother-infant pairs were studied. Breast milk was analyzed for nicotine using gas chromatography. Breast milk from smoking mothers contained a mean of 33.1 ng/mL of nicotine while the breast milk from nonsmoking mothers contained a mean of less than 6.45 ng/mL of nicotine. Infant physiologic measures were taken before and 20 min after breast-feeding. After breast-feeding, infants of smoking mothers had a significant change in respirations and oxygen saturation while infants of nonsmoking mothers had a significant change in pulse only. Results provide a scientific basis for counseling smoking, breast-feeding mothers.     

Changes of renal taurine transport after treatment with triiodothyronine or dexamethasone in amino acid loaded rats

In adult female anaesthetized rats, the influence of triiodothyronine or dexamethasone on renal amino acid (AA) handling was investigated in taurine (45 mg/100 g b.wt.) loaded animals. Bolus injections of taurine were followed by temporary increase in fractional excretion (FE(AA)) of taurine as well of the endogenous amino acids which were not administered. Under taurine load conditions, triiodothyronine treatment (20 microg/100 g b.wt. for 3 days, i.p. once daily) was followed by a slight stimulation of the renal taurine reabsorption: the increase in FE(taurine) after taurine load was lower than in untreated rats. Dexamethasone (60 microg/100 g b.wt. for 3 days, i.p. once daily) was without significant effect on FE(taurine) in taurine loaded rats. In non taurine loaded rats there was no hormone influence at all. Similarities and differences between the effects of bolus injections of taurine, glutamine, and leucine on the FE(AA) of these three amino acids were compared in detail to further clarify the reason for the increased amino acid reabsorption capacity after pretreatment with triiodothyronine or dexamethasone.     

Can active immunization redirect an anti-IgE immune response?

We used as a template a mouse monoclonal antibody against IgE to isolate peptides from random peptide phage display libraries. Thereby, two types of peptides were isolated that corresponded to two different epitopes on the human IgE molecule. These peptides, also called mimotopes, seem to be a suitable tool in conjunction with carriers to induce an autoimmune response with a beneficial effect in humans, because the originally used template antibody is capable of neutralizing IgE, is nonanaphylactogenic, and inhibits IgE synthesis. The vaccination approach is further supported by the fact that we were capable of isolating anti-idiotypic antibodies from antibody phage display libraries against the template antibody. These anti-idiotypic antibodies were inhibited by both of the isolated IgE mimotopes. Thus, active vaccination with defined IgE mimotopes may represent a follow-up drug for the presently used anti-IgE antibodies.     

Localized behavioral effects of vasopressin on maintenance of an active avoidance response in rats.

Four experiments employing a total of 148 male Wistar rats investigated the role of lysine vasopressin (LVP) in maintaining shock-avoidance behavior under extinction conditions; a pole-jump situation was used. In 3 experiments, a single injection of 1 μg LVP was administered to Ss on the 1st acquisition session. The following results were obtained: (a) Resistance to extinction occurred when LVP effects were restricted to a single correct response; (b) similar effects occurred when the injection was delayed until immediately after the trial; and (c) classical conditioning alone was a sufficient behavioral substrate for these effects, but instrumental conditioning was more effective. In Exp IV, 1 μg LVP produced increased resistance to extinction when given in association with behavior which accelerated extinction. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Passive immunization reduces immunity that results from simultaneous active immunization against tick-borne encephalitis virus in a mouse model

Concomitant administration of an antigen and antibodies of the respective specificity has been shown to result in reduced levels of actively produced antibodies. This has also recently been observed in a clinical trial on simultaneous passive and active immunization against tick-borne encephalitis virus (TBEV). In the current study the influence of simultaneous passive and active immunization on vaccine induced protective immunity against TBEV has been evaluated in a mouse model. Two immunizations with licensed whole-killed TBEV vaccines gave close to complete protection. Administration of human or mouse TBEV antibodies together with the first vaccine dose resulted in a significant reduction of vaccine induced protection against TBEV challenge. This effect was even more pronounced than that observed earlier on the levels of vaccine induced antibody.     

Passive-active immunization in infants of hepatitis Be antigen-positive mothers. Comparison of the efficacy of early and delayed active immunization

OBJECTIVE: To assess the efficacy of late active immunization against hepatitis B concomitant with diphtheria, pertussis, tetanus, and polio vaccine in high-risk infants receiving hepatitis B immune globulin at birth. DESIGN: Randomized study of infants born to mothers positive for hepatitis B surface antigen (HBsAg) and hepatitis Be antigen (HBeAg). SETTING: Three large city hospitals and one rural area providing prenatal care and obstetric services. SUBJECTS: Eighty neonates of HBsAg- and HBeAg-positive carrier mothers received 0.5 mL/kg of body weight hepatitis B immune globulin within 2 hours of birth and hepatitis B vaccine (10 micrograms) at 0, 1, 2, and 11 months of age (group A) or at 3, 4, 5, and 11 months of age concomitant with diphtheria, pertussis, tetanus, and polio immunization (group B). A second dose of hepatitis B immune globulin was given to infants on schedule B at 3 months. MAIN OUTCOME MEASURES: Blood samples were collected at 0, 3, 6, 11, and 12 months of age and tested for antibodies against hepatitis B core antigen and HBsAg. Follow-up visits were scheduled annually up to 5 years of age. RESULTS: Eight infants were excluded from analysis. During the study period, six children became HBsAg carriers, three in each group, which corresponds to a 5-year incidence of infection of 9% and 8% for groups A (three of 35) and B (three of 37), respectively. Subclinical infections (persistent anti-HBc positivity beyond month 12 or appearance of anti-HBc) were encountered in another eight infants (four in each group). CONCLUSION: Late active immunization starting at 3 months of age appears to provide similar protective efficacy as active immunization starting at birth when combined with hepatitis B immune globulin at 0 and 3 months of age.     

Active immunization alters the plasma nicotine concentration in rats

The ability of active immunization to alter nicotine distribution was studied in rats. Animals were immunized with 6-(carboxymethylureido)-(+/-)-nicotine (CMUNic) linked to keyhole limpet hemocyanin (KLH). Antibody titers determined by ELISA, using CMUNic coupled to albumin as the coating antigen, were greater than 1:10,000. Antibody binding was inhibited by neither of the nicotine metabolites cotinine and nicotine-N-oxide but was inhibited to a greater extent by CMUNic than by nicotine; this suggests the presence of antibodies to the linker structure as well as antibodies to nicotine. Antibody affinity for nicotine measured by soluble radioimmunoassay was 2.4 +/- 1.6 x 10(7) M-1, and binding capacity was 1.3 +/- 0.7 x 10(-6) M, which corresponds to 0.1 +/- 0.05 mg/ml of nicotine-specific IgG per milliliter of serum. One week after their second boost, groups of eight anesthetized rats immunized with either CMUNic-KLH or KLH alone received nicotine 0.03 mg/kg (equivalent to two cigarettes in a human) via the jugular vein over 10 sec. This dosing regimen was shown to mimic the arterio-venous nicotine concentration gradient typical of nicotine delivered by cigarette smoking in humans. Plasma nicotine concentrations at 10 to 40 min were 4 to 6-fold higher in the CMUNic-KLH rats than in controls (P < .001). Nicotine binding in plasma determined by equilibrium dialysis was markedly increased in the CMUNic-KLH group (83.4 +/- 6.8% vs. 16.4 +/- 14.2%), but brain nicotine concentrations at 40 min did not differ (37.9 +/- 4.5 vs. 44.0 +/- 8. 4 ng/g, CMUNic-KLH vs. KLH, P = .1). The amount of nicotine bound to antibody in plasma, estimated from the in vivo data, was 9% of the administered dose. These data demonstrate that active immunization can bind a significant fraction of a clinically relevant nicotine dose in plasma. Observing this effect with antibodies of modest affinity and titer is encouraging, but better immunogens may be needed to alter nicotine distribution to brain and modify nicotine's behavioral effects.     

Reciprocal effects of thyroxine and triiodothyronine on their deiodination by rat tissues in vitro

The reciprocal effects of loading doses of thyroxine (T4) or triiodothyronine (T3) on the deiodination of their 125iodine-labelled isotopes by rat muscle and liver homogenates were studied. In 21 experiments muscle homogenates deiodinated a mean 45.0% of a tracer dose of [125I]T4 and 18.0% of [125I]T3. On addition of graded amounts of nonradioactive T4 or T3 the percentual deiodination of both labelled hormones progressively declined. This effect was significantly greater in homogenates incubated with non-radioactive T4, thus reflecting a stronger affinity of this hormone for muscle deiodinating sites. This correlate with the greater displacment of [125I]T3 as revealed by the percentage of recovered labelled hormone. In 18 experiments liver homogenates deiodinated a mean 14.6% of a tracer amount of [125I]T4 and 8.5% of [125I]T3. The addition of a T4- or a T3-load was followed by a smaller decrease in percentual deiodination of both labelled hormones as compared to muscle homogenates. Unlike the effects observed in muscle, the breakdown of [125I]T4 and [125I]T3 by liver homogenates was equally affected by similar amounts of stable T4 or T3. It is concluded that in the present in vitro system T4 and T3 share cellular sites of deiodination in rat muscle and liver and that, at least in muscle, which constitutes over one-half of the rat body weight T4 appears to be preferentially deiodinated.     

Chronokinetics of active biliary ampicillin secretion in rats

To estimate the functional maturity of the phagocytic defence in neonatal calves, we analyzed the characteristics of blood phagocytes from calves (n = 10) 1 h post partum (p.p.) and 4 h p.p. At 1 h p.p., all calves were colostrum-deprived, while 5 calves had received colostrum before the 4 h p.p. sampling. The results were compared to those obtained from 3-9-week-old calves (n = 10). Phagocytic and oxidative burst activity of polymorphonuclear leukocytes (PMNL) and monocytes were determined in whole blood and separately analyzed by flow cytometry. In neonates prior to colostrum ingestion (1 h p.p.), phagocytic activity of PMNL against non-preopsonized E. coli was lower when compared to PMNL of 3-9-week-old calves. Opsonization of bacteria with pooled plasma from adult animals only partially restituted this lower PMNL phagocytic activity, indicating that humoral as well as cellular aspects of PMNL phagocytosis are altered in neonatal calves. In contrast to PMNL, monocytes of neonates exhibited an enhanced phagocytic activity. The oxidative burst activity of PMNL, as well as of monocytes was higher in newborn calves. During the first 4 h of life, the activities of blood phagocytes changed. Colostrum ingestion was accompanied by an increase in the percentage of phagocytizing PMNL and monocytes. This increase was absent in colostrum-deprived calves. In contrast, the oxidative burst activity of phagocytes decreased with age. In monocytes, the decrease of oxidative burst activity was only observed in colostrum-fed calves. In conclusion, some blood phagocyte functions in calves were found to be immature at birth, but these functions are presumably compensated by high absolute PMNL numbers and by other the more active mechanisms.     

Adjuvant effects of fluoride on oral immunization of chickens

The present study was conducted to examine the antibody responses of chickens after oral immunization and the influence of sodium fluoride (NaF) on their immunological states. Bovine serum albumin (BSA) was used as an antigen, and the response was measured by enzyme-linked immunosorbent assays of serum samples, bile samples, and lachrymal fluids. Oral immunization of chickens with antigen alone hardly induced antibody responses in sera, bile samples or lachrymal fluids. Moreover, compared to control chickens, these orally immunized chickens exhibited a lower serum IgG response to subsequent parenteral immunization, suggesting that oral immunization induced immunological tolerance in chickens. A mucosal adjuvant, NaF, could abrogate oral tolerance and elicit an increase in antibody responses. Chickens, which received oral administration of antigen and NaF simultaneously, showed a significant rise in serum IgG antibody. Although there were variations among individual chickens and the titers were low, IgA antibodies were detected in bile samples and lachrymal fluids.     

Regulation of gill cytosolic corticosteroid receptors in juvenile Atlantic salmon: interaction effects of growth hormone with prolactin and triiodothyronine

The potential effects of growth hormone (GH), prolactin (Prl), and triiodothyronine (T3) on gill Na+,K+-ATPase activity and corticosteroid receptor (CR) concentration (Bmax) and dissociation constant (Kd) were examined in juvenile Atlantic salmon (Salmo salar). Compared to controls, fish injected with GH (ovine, 5.0 microgram g-1) had significantly greater gill Na+,K+-ATPase activity after 7 and 14 days. Gill CR Bmax and Kd were significantly elevated on day 7, but not day 14. T3 also significantly increased CR Bmax. The effect of GH on CR Bmax was also additive with T3 (5.0 microgram g-1) treatment. There was a synergistic effect on CR Bmax when purified coho salmon GH (csGH, 0.1 microgram g-1) was injected in combination with T3 (1.6 microgram g-1). Prl (ovine, 5.0 microgram g-1; purified coho salmon, 0.1 microgram g-1) did not significantly alter gill CR Bmax. Although Prl limited the increase in CR Bmax by GH, the effect was not signicant. T3 and Prl did not have an effect on Kd. GH significantly increased gill Na+,K+-ATPase activity, T3 administration did not have a significant effect, and Prl-treated fish had significantly lower gill Na+,K+-ATPase activity. The results indicate that T3 acts additively with GH, while Prl has no effect in regulating CR Bmax. An increase in cytosolic CR by GH and T3, but not Prl, may regulate gill responsiveness to cortisol and be an important mechanism in the endocrine control of physiological changes during the parr-smolt transformation.     

Carry-over effects of dietary crude protein and triiodothyronine (T3) in broiler chickens

Indian River male broiler chickens growing from 7 to 30 d of age were fed on diets containing crude protein levels ranging from 120 to 300 g/kg plus 0 or 1 mg triiodothyronine (T3)/kg diet. The purpose of this study was to examine the effects of these treatments on lipogenesis after a common diet was fed (180 g crude protein/kg diet from 30 to 56 d of age). Dietary treatment groups were sampled at 30 and 56 d. In vitro lipogenesis was determined by incubating liver explants for 2 h at 37 degrees in Hanks' salts containing 25 mM-HEPES and 10 mM-[2-14C]acetate and then measuring acetate incorporation into total lipid. Growth and feed consumption from 7 to 30 d increased (P < 0.01) as dietary protein increased from 120 to 210 g/kg diet. Both measurements decreased as crude protein increased from 210 to 300 g/kg diet. T3 decreased (P < 0.01) growth and feed intake during this period. Low-protein (< 180 g/kg) diets increased (P < 0.05) and T3 decreased lipogenesis in 30-d-old chickens. Although birds given T3 from 7 to 30 d grew at the greatest rate from 30 to 56 d of age, the final body weight was still less than controls. In vitro lipogenesis at 56 d of age was not affected by either of the two dietary treatments. In contrast, the relative size of the abdominal fat pad (g/kg body weight) at 56 d was decreased by feeding T3 from 7 to 30 d. Any changes in metabolism elicited by either dietary protein levels or hormone treatments may be specific to the particular dosing interval and are not sustained when a common diet is fed during a repletion period.     

Comparison of tamoxifen effects on the actions of triiodothyronine or growth hormone in the ovariectomized-hypothyroid rat

Recent studies have suggested that a subset of estrogen responses arise via modulation of triiodothyronine (T3) actions, and depend on T3 for expression: other estrogen responses are not T3-dependent. Moreover, tamoxifen acts as a full estrogen agonist in T3-dependent responses but behaves as an antiestrogen in T3-independent responses. T3 directly induces a variety of metabolic enzymes and proteins, and also induces rat growth hormone (GH). Thus, some T3-dependent tamoxifen effects might reflect modulation of GH rather than T3 actions. To address this issue, tamoxifen effects on somatotropic and metabolic actions of T3 and GH were compared in ovariectomized rats with methimazole-induced hypothyroidism. Rats were given T3 (10 micrograms/kg/day) or ovine GH (2 mg/kg/day) with or without tamoxifen (0.5 mg/kg/day) for 30 days. GH was poorly effective in producing a sustained increase in somatic growth in hypothyroid rats compared to T3; nonetheless, GH effects to increase body weight, tibia length and serum insulin-like growth factor I while decreasing fat mass and evoking small increases in body temperature were not inhibited by tamoxifen. Tamoxifen also did not inhibit GH trends to increase tibia bone mineral density. T3 increased body temperature, insulin-like growth factor I levels and all measures of somatic growth and, unlike GH, increased food intake and tended to decrease tibia bone mineral density. Tamoxifen inhibited the somatotropic actions of T3 (including increases in insulin-like growth factor I levels), and produced significant increases in tibia bone mineral density only in T3-treated rats. Tamoxifen had no effect on T3 actions to increase food intake or body temperature. T3 alone increased fat mass and exhibited a tendency to decrease serum triglycerides: tamoxifen had no effect on these parameters in the absence of T3. However, coadministration of tamoxifen with T3 produced a marked decrease in fat mass and increased serum triglycerides. GH had no effect on serum triglycerides in either the presence or absence of tamoxifen. Serum glucose levels appeared normal in all groups. The data indicate that multiple tamoxifen effects on growth and metabolism may reflect modulation of T3 rather than GH actions.     

Effects of thyroxine as compared with thyroxine plus triiodothyronine in patients with hypothyroidism

BACKGROUND: Patients with hypothyroidism are usually treated with thyroxine (levothyroxine) only, although both thyroxine and triiodothyronine are secreted by the normal thyroid gland. Whether thyroid secretion of triiodothyronine is physiologically important is unknown. METHODS: We compared the effects of thyroxine alone with those of thyroxine plus triiodothyronine (liothyronine) in 33 patients with hypothyroidism. Each patient was studied for two five-week periods. During one period, the patient received his or her usual dose of thyroxine. During the other, the patient received a regimen in which 50 microg of the usual dose of thyroxine was replaced by 12.5 microg of triiodothyronine. The order in which each patient received the two treatments was randomized. Biochemical, physiologic, and psychological tests were performed at the end of each treatment period. RESULTS: The patients had lower serum free and total thyroxine concentrations and higher serum total triiodothyronine concentrations after treatment with thyroxine plus triiodothyronine than after thyroxine alone, whereas the serum thyrotropin concentrations were similar after both treatments. Among 17 scores on tests of cognitive performance and assessments of mood, 6 were better or closer to normal after treatment with thyroxine plus triiodothyronine. Similarly, among 15 visual-analogue scales used to indicate mood and physical status, the results for 10 were significantly better after treatment with thyroxine plus triiodothyronine. The pulse rate and serum sex hormone-binding globulin concentrations were slightly higher after treatment with thyroxine plus triiodothyronine, but blood pressure, serum lipid concentrations, and the results of neurophysiologic tests were similar after the two treatments. CONCLUSIONS: In patients with hypothyroidism, partial substitution of triiodothyronine for thyroxine may improve mood and neuropsychological function; this finding suggests a specific effect of the triiodothyronine normally secreted by the thyroid gland.     

Physiologic studies of spinal inhibitory circuits in patients with stiff-person syndrome

Human protoporphyria results from mutations in the ferrochelatase gene. Heritable deficiency of ferrochelatase causes overproduction of protoporphyrin IX, principally in the erythron. Photosensitivity is a universal feature of protoporphyria but hepatic clearance of the hydrophobic protoporphyrin molecule with excretion in bile may lead to precipitation within biliary pathways. Thus cholestatic injury and protoporphyrin gallstones occur. Minor hepatic abnormalities are frequent, but at least 30 patients have been reported with a progressive liver disease that requires transplantation. Fulminant hepatic disease appears to be recessively inherited in some pedigrees. Hazards of liver transplantation include tissue photolysis, hemolysis, and an unexplained neurological syndrome, but most of the 15 patients reported after transplantation have survived for several months to > 6 years. Aspects of protoporphyria, its pathogenesis and contemporary therapeutic strategies are considered, with emphasis on hepatic sequelae.     

Physiologic effects of cisapride on gastric emptying after pylorus-preserving gastrectomy for early gastric cancer

Pylorus-preserving gastrectomy (PPG) has been considered reasonable reduction surgery. However, even patients in whom more than 1 year passed after surgery frequently have a feeling of gastric fullness after meals and long-term retention of foods in the residual stomach. To treat this syndrome, cisapride has been administered. We studied the emptying time of a semisolid diet (radioisotope method using 99mTc-tin colloid-labeled rice gruel) and the emptying time of a fluid diet (acetaminophen method with orange juice) before and after oral administration of cisapride (15 mg/day for 1 month) in 14 patients (10 men, 4 women; 32-70 years old, average 60.6 years) who underwent PPG (Billroth I procedure, D2 lymph node dissection, curability A) for treatment of early gastric cancer. Ten healthy volunteers without gastrointestinal symptoms and digestive diseases (7 men, 3 women; 28-61 years old, average 49.8 years) were enrolled as controls. The results showed obviously delayed emptying time of the semisolid diet before administration of cisapride in patients with PPG compared with that of the control group, whereas the emptying curves for the fluid diet showed an almost normal pattern. One month after the start of cisapride administration the emptying time of the semisolid diet was improved, and the emptying curves were close to the patterns in the control group. Emptying of the fluid diet was slightly accelerated compared with that before administration of cisapride, and the emptying curves showed almost the same pattern as in the control group. A postgastrectomy symptom, "gastric fullness," after PPG was alleviated by cisapride. These results showed that cisapride improved delayed emptying of a semisolid diet after PPG and prevented the feeling of gastric fullness after meals due to retention in the residual stomach.