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PubMed1988

Calcitonin gene-related peptides I and II and calcitonin: distinct effects on gastric acid secretion in humans.

The human calcitonin gene-related peptides I and II (CGRP I and CGRP II) are two neuropeptides that have been recognized throughout the gastrointestinal system including the stomach. The present study was undertaken to compare in healthy volunteers the effects of intravenous infusions of CGRP I and CGRP II (79 pmol/kg.h) on pentagastrin-stimulated acid secretion to those of calcitonin (88 pmol/kg.h). Calcitonin gene-related peptide I did not inhibit basal or pentagastrin-stimulated acid secretion. However, CGRP II and calcitonin inhibited pentagastrin-stimulated acid responses by 20% and 28%, respectively (p less than 0.05 and p less than 0.01), whereas basal acid output was only reduced with calcitonin (p less than 0.05). These effects were recognized with low doses of pentagastrin, and absent with high doses suggesting competitive inhibition. Furthermore, step-doses of CGRP I and CGRP II (79-320 pmol/kg.h) were given intravenously on continuous pentagastrin stimulation and compared with calcitonin (88-352 pmol/kg.h). Calcitonin gene-related peptide II and calcitonin induced a dose-dependent decrease of acid output, whereas CGRP I was ineffective. The inhibitory effects of CGRP II and calcitonin are not due to increased gastric alkaline secretion or to somatostatin release, as neither peptide stimulated gastric bicarbonate secretion or induced an increase in circulating somatostatin. In conclusion, CGRP II, unlike CGRP I, inhibits gastric acid secretion in humans. Inhibitory effects of CGRP II and of calcitonin were comparable. The results imply that CGRP I and II, at the level of the stomach, have distinct biological properties in humans.

Adult↗
PubMed1990

Central action of recombinant interleukin-1 to inhibit acid secretion in rats.

The influence of recombinant human interleukins-1 beta and -1 alpha and rat interleukin-1 beta on gastric acid secretion was investigated in awake rats with pylorus ligation. IC injection of either human interleukin-1 beta, human interleukin-1 alpha, or rat interleukin-1 beta induced a dose-dependent inhibition of gastric acid output. At IC doses less than 100 ng, human interleukin-1 beta was more effective than the other forms or sources of interleukin-1, whereas at higher doses (100-500 ng), human interleukins-1 beta and -1 alpha and rat interleukin-1 beta were equipotent. The inhibitory effect was observed 30 minutes after interleukin-1 injection and maintained throughout the 6-hour experimental period. IC injection of interleukin-1 beta inhibited vagally stimulated gastric acid secretion induced by IC injection of the stable thyrotropin-releasing hormone analogue RX 77368. Indomethacin (1, 5, and 10 mg/kg, IP, -30 minutes) induced a dose-related prevention of the inhibitory effect of IC interleukin-1 beta. IC injection of the corticotropin-releasing factor antagonist alpha-CRF9-41, bilateral adrenalectomy, and noradrenergic blockade with bretylium did not influence the antisecretory effect of interleukin-1. Polypeptide action was not related to changes in circulating gastrin levels. Human interleukin-1 beta injected IV also inhibited gastric acid secretion, but the peripheral dose required to induce a significant effect was 10(3)-fold higher than when given centrally. These results show that IC interleukin-1 beta acts centrally to induce a long-lasting inhibition of gastric acid secretion, and this effect requires the integrity of prostaglandin pathways. These data suggest a possible interaction between the immune and gastrointestinal systems.

Animals↗
PubMed1991

Presence of embryotoxic factor in the sera of neonates affected by myelomeningocele: a study on chick embryo.

An experimental study on chick embryos was conducted where 0.02 mL of serum, taken from five neonates (1 to 7 days of age) with myelomeningocele was injected separately into the fertile white leghorn eggs, at zero hour of incubation. A total of 150 experimental and 135 control eggs were injected. It was observed that the embryos of chick exposed to experimental serum had an increased frequency of embryonic death and/or gross abnormalities as compared with the control group (chi 2 = 32.07; P less than .001). The anomalies observed were those of neural tube, gastrointestinal system, and musculoskeletal system. In addition, there was a generalized growth retardation among experimental embryos. These malformations are probably due to an embryotoxic factor, which is present in the serum of the baby with myelomeningocele and has been transmitted transplacentally.

Animals↗
PubMed1992

Hirschsprung's disease: associated abnormalities and demography.

We here examine the demographic parameters of patients with Hirschsprung's disease. The study population includes all patients with histologically confirmed disease treated at the Children's Hospital Medical Center of Boston over the 25-year period extending from 1961 through the first quarter of 1986. There were 179 cases. Overall, children with Hirschsprung's disease were found less likely to be first born (P less than .01). This relationship was seen to persist irrespective of maternal age, maternal race, or type of disease. The implications of this finding are discussed. Overall, 22% of these children had one or more associated abnormalities involving the neurological, cardiovascular, urological, and gastrointestinal systems. Many of the disorders appeared to be related to neurocrestopathies. Frequent associations included Down's syndrome, defects in cardiac septation, tetralogy of Fallot, and Dandy-Walker syndrome. These conditions occurred more frequently than would have been predicted through chance alone. This study found no association between an increased maternal age and the occurrence of Hirschsprung's disease. This study also found that approximately 7% of the affected children had been born prematurely.

Abnormalities, Multiple↗
PubMed1994

Spinal anesthesia for primary repair of gastroschisis: a new and safe technique for selected patients.

Spinal anesthesia has been described for infants and premature babies undergoing minor operative procedures. The advantages of shorter operating time, avoidance of intubation, and shorter hospital stay have made this the gold standard for premature and other high-risk infants requiring minor procedures. However, little is known about this technique for major interventions in newborns and preterm infants. Recently, four infants born with gastroschisis underwent repair under spinal anesthesia. Two had accompanying intestinal atresia (one with a prenatal perforation and pan-hypopituitarism), and two had intact gastrointestinal systems. The gestational ages were 39, 33, 36, and 36 weeks, respectively. All had primary closure of the defect; one had no repair of the atresia because the bowel was thick and matted with a significant peel, and the defect was not identified. In the second case with atresia, necrosis and perforation of a localized segment of intestine was identified proximal to the intestinal atresia, and was exteriorized with the primary repair. When they arrived in the operating room, all four infants were breathing spontaneously, on room air, after appropriate fluid resuscitation. All underwent spinal anesthesia, which was the only agent used for the operation. The operative time was 45, 25, 30, and 25 minutes, respectively (mean, 31.25 minutes). The duration of anesthesia was 170 to 230 minutes (mean, 205 minutes). All infants were returned to the neonatal intensive care unit on room air and breathing spontaneously. One was given morphine postoperatively and suffered significant respiratory depression, requiring intubation. It appears that spinal anesthesia is safe and effective for major operative procedures in high-risk infants. (ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Muscles↗
PubMedDate not supplied

Cholecystokinin in psychiatric research: a time for cautious excitement.

Cholecystokinin (CCK) is a peptide neurotransmitter that was originally isolated from the gastrointestinal system, but which is extensively and abundantly distributed within the central nervous system (CNS). Stimulated by the fairly recent recognition of receptor subtypes (A and B), and the development of receptor-specific antagonists, CCK research has been advancing rapidly; and its potential importance to psychiatric neuroscience has been increasingly recognized. CCK participates in the mediation of satiety; it interacts with dopamine and may modulate psychosis; it interacts with opiate systems and may be an "anti-analgesic": and it appears to play a role in the mediation of anxiety. Highly specific, CCK-B receptor antagonists have reached clinical trials and have potential clinical utility as anxiolytics, antipsychotics, anti-anorexics, or analgesics. There are grounds for excitement, but many obstacles remain to be overcome and clinical potential may not be fulfilled. However, we must not allow clinical disappointments to slow the accelerating pace of scientific progress in CCK research. Regardless of clinical payoffs, the CCK receptor is clearly of great importance to human CNS functioning and deserves ongoing scientific attention.

Anxiety Disorders↗
PubMed1986

Regulation of interleukin-1 production in murine macrophages and human monocytes by a normal physiological constituent.

The in vitro production of large quantities of interleukin-1 (IL-1) in mouse peritoneal exudate macrophages and human peripheral blood monocytes is possible through the use of the proteolytic enzyme pepsin and its zymogen pepsinogen. Equal amounts of IL-1 are generated by pepsin in the absence or presence of polymixin B. The addition of pepsin or pepsinogen had no effect on the proliferation of C3H/HeJ thymocytes to the plant mitogen phytohemagglutinin. Pepsin and pepsinogen are present in significant quantities in immune cells and the plasma. Although little is known concerning the physiological role of pepsin and pepsinogen outside of the gastrointestinal system, it may be proposed that the in vivo production of IL-1 may in part be regulated by the cellular and plasma concentrations of pepsin and pepsinogen.

Animals↗
PubMed1995

Blockade of digestion by famotidine pretreatment does not interfere with the opioid-enhancing effect of ingested amniotic fluid.

Ingestion of placenta or amniotic fluid by rats has been shown to enhance ongoing opioid-mediated antinociception, but does not, by itself, produce antinociception. This enhancement is produced by an active substance(s) in placenta and amniotic fluid that we have termed POEF for placental opioid-enhancing factor. Previous research has shown that enhancement requires mediation by the gastrointestinal system: gastric vagotomy blocks enhancement produced by ingested placenta; amniotic fluid injected SC or IP does not produce enhancement. The present study was designed to distinguish between two possible explanations for the blockade of the POEF effect produced by gastric vagotomy: that afferent information arising in vagal gastric receptors conveys the critical information to the CNS, or that disruption of vagal efferent action on digestion blocks the manufacture or activation of the POEF molecule in the gut. Famotidine is an H2-histamine receptor antagonist that reduces gastric acid and pepsin secretion to an extent at least as great as gastric vagotomy. Rats treated with either famotidine or a vehicle were fed placenta or a control substance, then stimulated with vaginal/cervical probing to produce antinociception that is partly opioid mediated. Famotidine did not block POEF enhancement of vaginal/cervical stimulation-induced analgesia in a tail flick latency test. These results suggest that enhancement by POEF does not require normal digestive processes or other processes inhibited by famotidine.

Amniotic Fluid↗
PubMed1984

The uptake and distribution of [3H]benzo[a]pyrene in the Northern pike (Esox lucius). Examination by whole-body autoradiography and scintillation counting.

The uptake and distribution of the polyaromatic hydrocarbon benzo[a]pyrene in Northern pike (Esox lucius) were investigated by whole body autoradiography and scintillation counting. [3H]Benzo[a]pyrene was administered either in the diet or in the water. The levels of this xenobiotic employed corresponded to levels found in moderately polluted water. The uptake and distribution of this compound and its metabolites were followed from 10 hr to 21 days after the initial exposure. The autoradiography patterns observed here with both routes of administration suggest, as expected, that benzo[a]pyrene is taken up through the gastrointestinal system and the gills, metabolized in the liver, and excreted in the urine and bile. Other findings indicate that the gills may not be a major route of excretion for benzo[a]pyrene and its metabolites in the Northern pike; that benzo[a]pyrene may be taken up from the water directly into the skin of this fish; that benzo[a]pyrene and its metabolites are heterogeneously distributed in the kidney of the Northern pike; and that very little radioactivity accumulates in the adipose tissue. With scintillation counting, uptake of radioactivity from the water was found to occur rapidly in all organs, reaching a plateau in most cases after about 0.8 days. The concentrations of radioactivity in different organs ranged between 50 (many organs) and 80,000 (gallbladder + bile) times that found in the surrounding water. Since most of the radioactivity recovered in different organs of the pike after 8.5 days of exposure was in the form of metabolites, we feel that metabolism may play an important role in the bioconcentration of xenobiotics in fish.

Animals↗
PubMedDate not supplied

Current concepts in infant nutrition.

Nutritional needs vary during the first year of life according to the infant's individualized pattern of growth and amount of physical activity. After delivery, the infant must make many physiologic adjustments, develop immunologic defenses, and take in adequate nutrients for survival. The type and consistency of foods change as the gastrointestinal system matures and becomes able to metabolize the components and excrete the needed metabolites of increasingly complex foods. The recommended dietary allowance for infancy is based on the amount of nutrients provided to healthy infants in human milk during the first six months of life and on the consumption of formula and increasing amounts of solid food during the second six months. The introduction of solid foods should parallel the developmental changes that occur within the central nervous system throughout the first year; these provide a level of readiness for the infant to manage foods of various textures from full liquid to soft. Even though significant technologic advances have led to changes in the way infants can be fed, human milk is still the optimal choice. Most women can be encouraged to breast-feed regardless of their own nutritional status or dietary intake. Contraindications can be managed on an individual basis. If women do not elect to breast-feed, suitable commercial formulas are available. The important issue in feeding is that of providing a variety of appropriately prepared foods offered in a nonjudgmental atmosphere so that the foundation is laid for the development of good food habits.

Bottle Feeding↗
PubMed1988

Review of chemical sensors for physiological measurement.

The continuous measurement of chemical species is important for physiological and biochemical research and for critical care medicine. Chemical sensors are being developed for the measurement of a wide range of analytes, especially gases, vapours, ions, catabolites, drugs and hormones. The mechanical form of these sensors may be adapted for use in single cells, tissue fluid and blood vessels, on the skin surface, in the respiratory and gastrointestinal systems. Optical and electro-chemical principles are now used widely for sensor design, and advances in electronic fabrication methods and in optical fibres, sources, and detectors, have been important.

Chemistry, Clinical↗
PubMed1988

Conformational analysis of possible biologically active (receptor-bound) conformations of peptides derived from cholecystokinin, cerulein and little gastrin and the opiate peptide, Met-enkephalin.

Possible biologically active (receptor-bound) conformations of peptides derived from cholecystokinin (CCK) have been deduced using conformational analysis combined with comparative studies of their biological specificities. Two peptides, the completely active carboxyl terminal heptapeptide from CCK (CCK-7), whose sequence is Tyr-Met-Gly-Trp-Met-Asp-Phe-NH2, and the carboxyl terminal heptapeptide from cerulein (CER-7) which has the same sequence as for CCK-7 except for replacement of Met 2 with a Thr 2, both stimulate peripheral receptors in gall bladder, pancreas, and pylorus in the gastrointestinal system. In contrast, two other very similar peptides, the last four residues of CCK (CCK-4) whose sequence is Trp-Met-Asp-Phe-NH2, and the carboxyl terminal hexapeptide of little gastrin (LGA-6, Tyr-Gly-Trp-Met-Asp-Phe-NH2, i.e., residue 2 deleted relative to CCK-7 and CER-7 sequences), interact specifically with gastrin receptors and not at all or very weakly with peripheral receptors. All of these peptides react with CCK receptors in the central nervous system, especially in forebrain. The results in the GI tract suggest that the peptides active on peripheral receptors adopt structures that are significantly different from those of the peptides that interact with gastrin receptors. We have generated all of the many low energy conformations for each of these peptides. By retaining only the conformations that are the same for peptides within the same group and then rejecting those resulting conformations that are the same for the peptides in the two different groups, we can greatly reduce the possible active conformations for the peptides within each class.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1995

Effect of PACAP on gastric acid secretion in rats.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a new VIP-like brain-gut peptide. Its effects on the motility and secretory functions of the gastrointestinal system have been shown in previous studies. In this study we investigated the effect of intravenous PACAP on gastric acid secretion in conscious pylorus-ligated rats and in gastric fistula rats. PACAP showed significant inhibitory effects on pentagastrin- and histamine-stimulated gastric acid secretion, but no effect on basal or carbachol-stimulated secretion in pylorus-ligated rats. It did show dose-related inhibitory effects both on basal gastric acid secretion and on secretion stimulated by pentagastrin, histamine, or carbachol in gastric fistula rats. PACAP did not alter serum gastrin levels. Inhibition of prostaglandin synthesis with indomethacin and immunoneutralization of somatostatin with anti-somatostatin serum did not prevent the inhibitory effect of PACAP on gastric acid secretion in pylorus-ligated rats. We conclude that PACAP most likely has a direct effect on parietal cells and that this effect may be mediated, at least partially, by inhibition of the action of histamine on parietal cells.

Adenylyl Cyclases↗
PubMed1982

Identity of ultrastructural effects of mercuric chloride and methyl mercury after intracerebral injection.

In man the clinical patterns of inorganic and organic mercury toxicity are different. Inorganic mercuric chloride mainly affects the renal and gastrointestinal systems. The characteristic neurological feature is a fine tremor, particularly of the hands and fingers. In contrast organic methyl mercury toxicity results in an exclusively neurological disorder, the characteristic features being ataxia, dysarthria, paresthesia and tunnel vision. To study the action of these classes of mercury compounds on neurones small amounts of mercuric chloride or methyl mercuric acetate were injected or iontophoresed into the rat cerebrum. The ultrastructural changes which followed were identical. Progressive and often pronounced cytoplasmic swelling of neurones suggested a defect at the cell membrane level. Thus is spite of their distinctive clinical syndromes these 2 classes of mercury compounds are capable of inducing neuronal necrosis.

Animals↗
PubMed1991

Cervical stump carcinoma.

Although supracervical hysterectomy is becoming a vanishingly rare procedure, there are still many women with a retained cervical stump. We have reviewed 70 patients treated at the Radiation Oncology Center, Mallinckrodt Institute of Radiology for carcinoma of the cervical stump. The average time between the hysterectomy and the diagnosis of cancer in the stump was 26.6 years. The median age at diagnosis of 63.5 years is 8.5 years older than the median age at diagnosis of patients with cancer of the cervix with an intact uterus. Patients were treated with external beam radiation and/or intracavitary implants. Sixteen patients underwent surgery as well. The 5- and 10-year overall actuarial survival for all patients was 60% and 40%, respectively. The 5- and 10-year progression-free survival for all patients was 77% and 70%, respectively. Ten-year progression-free survival by stage was: 0--100%, 1A--100%, 1B--79%, 2A--100%, 2B--66%, and 3B--39%. Poor histologic differentiation correlated with a decreased long-term progression-free survival. Black patients, and those receiving prolonged courses of external beam irradiation, had a trend toward a worse prognosis. Neither non-squamous histology nor gross appearance affected outcome. With a median follow-up time of 12.9 years, there were only three isolated local failures and four combined with distant metastases. Complications were few, with twice as many occurring in the gastrointestinal system as in the genitourinary tract. We conclude that carcinoma of the cervical stump effectively treated by radiation therapy yields results equivalent to those seen in patients with an intact uterus.

Adult↗
PubMed1985

Uptake and vascular transport of ingested aflatoxin.

The uptake and vascular transport of abomasally instilled aflatoxin B1 (AFB1) was investigated in sheep. Aflatoxin uptake was compared with that of palmitate, a water-insoluble oil known to be absorbed into the intestinal lymphatic drainage which bypasses the liver to enter the peripheral vascular circulation via the thoracic duct. After instillation into the abomasum, aflatoxin was detected in inferior vena cava blood within 30 min, while palmitate was not detected in vena cava blood at any time. Palmitate was detected in thoracic duct lymph after about 2 h. More than 95% of the palmitate in lymph was associated with the chylomicron fraction, while aflatoxin in either plasma or lymph was not detectably associated with any of the circulating lipoproteins. In addition, aflatoxin did not partition into plasma or lymph lipoproteins in vitro. Toxic lipophilic xenobiotics, such as benzo(a)pyrene and polychlorinated biphenyls (PCBs) do partition into lipoproteins, are absorbed into the intestinal lymphatic drainage, bypassing the liver to enter the peripheral vascular circulation directly, and are not specifically hepatotoxic. These data suggest that the mode of aflatoxin absorption from the gastrointestinal system results in its immediate transport to the liver, which may contribute to aflatoxin hepatotoxicity.

Aflatoxin B1↗
PubMed1988

Traditional Chinese medicine and the search for new antineoplastic drugs.

The experience of traditional Chinese medicine affords a valuable approach in the search for new antineoplastic drugs as illustrated by indirubin from Dang Gui Lu Hui Wan, irisquinone from Iris lactea pallasii and Zhuling polysaccharide from Polyporus umbellata. The application of chemotaxonomic principles to related species of those plants used in folk medicine has also provided an approach which can be used successfully for the development of new drugs. The studies of Cephalotaxus hainanesis and Camptotheca accuminata provide two typical examples in this regard. One must be aware that the experience of traditional Chinese medicine cannot be used without elaborate efforts in many cases. For example, the ancient Chinese ideograph for spleen does not mean spleen in the modern sense, instead it refers to the entire gastrointestinal system. Similarly, the ancient ideograph for kidney does not mean kidney in the modern sense, and can mean the entire endocrine system. Therefore, for the reasonable utilization of traditional Chinese medicine, one must be familiar with its basic concepts and terminology. In addition, one must bear in mind that the term "tumor" in folk medicine is applied to a very wide range of pathological manifestations which sometimes have no relation to the various forms of neoplasia. It is important for drugs and treatments to be analyzed carefully in modern terms to eliminate the false and to utilize the true information. Only in such a way can the experience of traditional medicine be integrated into modern medicine and make its contribution in the advancement of health care in the world.

Animals↗
PubMed1994

Salvia divinorum and salvinorin A: new pharmacologic findings.

The diterpene salvinorin A from Salvia divinorum (Epling and Jativa-M), in doses of 200-500 micrograms produces effects which are subjectively identical to those experienced when the whole herb is ingested. Salvinorin A is effectively deactivated by the gastrointestinal system, so alternative routes of absorption must be used to maintain its activity. Traditionally the herb is consumed either by chewing the fresh leaves or by drinking the juices of freshly crushed leaves. The effects of the herb when consumed this way depend on absorption of salvinorin A through the oral mucosa before the herb is swallowed.

Abietanes↗