[Adjuvant therapy in neonatal sepsis].
Explore the source record for details and available documents.
Bacterial Infections↗
Biomedical subjects
R Castro
Publications and source records attributed to R Castro.
Successful treatment of a giant cavernous hemangioma with oral cyclophosphamide (cytoxan) in an infant.
Explore the source record for details and available documents.
Administration, Oral↗
Prenatal haloperidol treatment decreases nerve growth factor receptor and mRNA in neonate rat forebrain.
Pregnant rats were treated daily with haloperidol (2 mg/kg) for 11 days until 1 day before birth. The levels of nerve growth factor (NGF), its receptor (NGFR) and NGFR-mRNA were measured in forebrain of 2-day old postnatal rats. Using Northern blot analysis, we observed a decrease in NGFR-mRNA. Furthermore, in binding studies, Kd and Bmax of treated rats were lower than in controls, but only in the low affinity binding sites. However NGF and its mRNA did not change after haloperidol treatment. In conclusion, our results suggest that prenatal haloperidol treatment can modify the development of forebrain cells, by changing NGFR expression.
Animals↗
Fetal brain serotonin synthesis and catabolism is under control by mother intake of tryptophan.
Previous morphological studies reported that serotonergic neurons appear in rats in the second half of prenatal life. Initially the biochemical differentiation of these neurons before birth was studied. Both serotonin (5-HT) and 5-hydroxyindole acetic acid (5-HIAA) was detected in the fetal brain on day 15 of gestation. During prenatal development an increase was detected in the brain levels of 5-HT (200% higher on day 19 than on day 15) and 5-HIAA (700% higher on day 19 than on day 15). Oral administration of tryptophan to pregnant rats induced a dose-related increase of tryptophan concentration in different fetal tissues, including brain. The increase in tryptophan tissue concentration was detected for low doses (50 mg/kg) and remained unsaturated after administration of high doses (1000 mg/kg). This observation suggests that the placental barrier is not effective to block the influx of high levels of tryptophan to the fetus. Tryptophan concentration in the brain is 300% higher than in the carcass and 600% higher than in the placenta. These data suggest a mechanism to assume a role in concentrating of tryptophan in the brain. Finally, it was found that an increase in brain tryptophan induced changes in both serotonin and 5-HIAA brain levels, but did not modify tyrosine, dopamine or norepinephrine levels. Thus, under physiological conditions, tryptophan hydroxylase activity in prenatal brain is probably not saturated by its substrate tryptophan.
Animals↗
Transplants of fetal substantia nigra regulate glutamic acid decarboxylase gene expression in host striatal neurons.
Lesions of the dopaminergic innervation to the striatum result in increased activity of glutamic acid decarboxylase (GAD) and increased GAD mRNA in striatal GABAergic neurons. Here we show that solid transplants of dopamine-containing fetal mesencephalic tissue placed adjacent to the striatum can completely reverse the elevation of GAD mRNA in the striatum of adult rats with complete lesions of the nigrostriatal dopamine projections. The ability of the fetal transplants to re-establish control over gene expression in host target neurons indicates that there is a significant transneuronal influence of the transplanted neurons. Furthermore, striatal GAD mRNA levels appear to be a good marker of the functional impact of dopamine-producing transplants.
Animals↗
Apomorphine lowers dopamine synthesis for up to 48 h: implications for drug sensitization.
Previous reports have shown that tolerance or sensitization to apomorphine depends on the dosage interval. The effect of apomorphine on behaviour increases when there is a drug-free period between successive injections. Here we studied the biochemical action of apomorphine during a drug-free period. The experiments showed that dopamine level and dopamine turn-over are persistently inhibited for at least 48 h after apomorphine administration. At 24 h after drug injection, there was a decrease of both DOPAC level and tyrosine hydroxylase activity. The results suggest that apomorphine induces long-lasting dopaminergic inhibition action that increases drug-induced behavioural response, perhaps after development of postsynaptic hypersensitivity.
3,4-Dihydroxyphenylacetic Acid↗
Ovine fetal renal and hormonal responses to changes in plasma epinephrine.
Circulating epinephrine alters atrial natriuretic factor (ANF) and arginine vasopressin (AVP) secretion, and all three hormones influence renal function. To quantify the relationships among fetal plasma epinephrine levels, fetal ANF and AVP secretion, and fetal renal function, six chronically catheterized fetal lambs (132 +/- 1 days gestation) received successive 40-min epinephrine infusions (0.1, 0.4, and 1.8 micrograms.min-1.kg-1). The second epinephrine infusion dose evoked significant increases in urine flow (V; 0.7 +/- 0.2 to 1.2 +/- 0.2 ml/min), free water clearance (CH2O; 0.3 +/- 0.1 to 0.7 +/- 0.1 ml/min), glomerular filtration rate (GFR; 3.9 +/- 0.7 to 5.4 +/- 0.8 ml/min), fractional water excretion (V/CH2O; 19 +/- 3 to 25 +/- 2%), mean arterial pressure (MAP; 45 +/- 3 to 51 +/- 4 mmHg), and a 94% increase in plasma ANF levels. A fourfold increase in the infusion dose significantly increased osmolar clearance (0.3 +/- 0.1 to 0.6 +/- 0.1 ml/min), sodium excretion (28 +/- 8 to 53 +/- 13 mueq/min), and plasma AVP levels (2.4 +/- 0.5 to 6.4 +/- 2.4 pg/ml) with no additional effect on V, CH2O, GFR, V/GFR, MAP, or plasma ANF levels. Urine osmolality and fractional sodium excretion did not change in response to epinephrine infusion. Our results demonstrate that epinephrine infusion stimulates fetal ANF secretion and to a lesser extent AVP secretion and significantly influences fetal renal function.
Animals↗
Fetal renal response to atrial natriuretic factor decreases with maturation.
The presence of atrial natriuretic factor (ANF) in fetal tissues and plasma early in gestation suggests that ANF may have a physiological role in cardiocirculatory homeostasis in utero. However, reported responsiveness of the fetal kidney to ANF varies markedly. To characterize the ontogeny of fetal renal responsiveness to ANF, chronically catheterized ovine fetuses at 114 +/- 1 days (n = 6) and 131 +/- 1 days (n = 6) received successive (30 min each) intravenous infusions of ANF at rates of 5, 25, and 100 ng.min-1.kg-1. Mean (+/- SE) fetal plasma ANF levels increased from 328 +/- 54 to 1,866 +/- 482 and 521 +/- 135 to 1,579 +/- 295 pg/ml in the younger and more mature fetuses, respectively. Mean urine volume (0.17 +/- 0.03 to 0.37 +/- 0.09 ml.min-1.kg-1) and GFR (0.9 +/- 0.2 to 1.8 +/- 0.4 ml.min-1.kg-1) increased in the early gestation fetuses but did not change in the older fetuses. Mean urine sodium excretion and osmolar clearance increased by 352 and 155% in the early gestation fetal lambs and 118 and 50% in the older animals. The fetal plasma ANF clearance rates (PCANF) were lower in the early vs. the late gestation fetuses (68 +/- 15 vs. 116 +/- 28 ml.min-1.kg-1, respectively). These results demonstrate a decrease in fetal renal responsiveness to ANF with advancing fetal age. Multiple factors appear to contribute, including changes in PCANF and maturational changes in glomerular filtration rate, renal tubular function and ANF receptor metabolism.
Animals↗
Ontogeny of atrial natriuretic factor receptors and cyclic GMP response in rabbit renal glomeruli.
Atrial natriuretic factor (ANF) has been identified in fetal and newborn mammals, and considerable data regarding fetal ANF metabolism are available. However, there is limited information concerning ANF receptors or receptor ontogenesis in developing mammals. We measured ANF receptor binding capacity, affinity, and ANF-induced cyclic GMP (cGMP) generation in isolated renal glomeruli from fetal (29 d gestation, term = 31 d), newborn (3 d), juvenile (28 d), and adult rabbits. The (mean +/- SEM) glomerular receptor binding capacity values for ANF in fetal and newborn animals (10 +/- 1 and 12 +/- 3 fmol/mg protein) were similar and significantly lower than the values for juvenile and adult animals (30 +/- 8 and 74 +/- 15 fmol/mg protein, respectively). In contrast, there were no significant differences in ANF receptor affinity values or dose-dependent increases in ANF-stimulated cGMP generation among the age groups studied. In competition studies, we observed effective displacement of 125I-ANF by C-ANF4-23, a ring-deleted ANF analogue, in adult, juvenile, and newborn glomeruli; however, C-ANF displaced only about 50% of the 125I-ANF in fetal tissue. The addition of C-ANF did not elicit cGMP generation, nor did C-ANF affect ANF-induced cGMP generation in fetal, newborn, or adult glomeruli. These results indicate that 1) the ANF receptor-guanylate cyclase system is intact in 29-d fetal rabbit glomeruli, and 2) the ANF-induced cGMP formation is similar in fetal and adult animals, whereas receptor binding capacity is relatively higher in adult glomeruli. These results suggest a higher proportion of nonguanylate cyclase-coupled ANF receptors in the mature rabbit.
Age Factors↗
Effect of a ring-deleted atrial natriuretic factor analogue on ovine fetal renal and cardiovascular function.
The proposed actions of atrial natriuretic factor (ANF) are mediated through specific plasma membrane (R1) receptors coupled to guanylate cyclase. A second receptor, R2, has been characterized by its ability to bind to an acyclic, truncated ANF analog (C-ANF4-23). The ANF-R2 receptor has not been identified in the fetus. Our study was conducted to determine the effects of C-ANF on fetal renal and cardiovascular function and plasma ANF clearance rates. Chronically catheterized ovine fetuses (n = 6) at 111 to 117 d gestation (term 145 d) received a C-ANF infusion (1 microgram/min/kg) for 30 min followed by a combined infusion of C-ANF and ANF (C-ANF, 1 microgram/min/kg; ANF, 100 ng/min/kg) for an additional 30 min. C-ANF infusion significantly increased (mean +/- SEM) plasma ANF concentration (437 +/- 45 to 1067 +/- 297 pg/mL), urinary flow rate (0.26 +/- 0.04 to 0.38 +/- 0.07 mL/min/kg), sodium excretion (12.9 +/- 3.5 to 21.7 +/- 6.1 mumol/min/kg), and osmolar clearance (0.14 +/- 0.02 to 0.21 +/- 0.04 mL/min/kg) (p less than 0.05). The combined C-ANF/ANF infusion further increased plasma ANF concentration to 2394 +/- 532 pg/mL and resulted in significant increases in urinary flow rate, sodium excretion, osmolar clearance, GFR, and free water clearance compared with C-ANF infusion alone (p less than 0.05). These renal responses, however, were not significantly different from the responses to ANF infusion alone (100 ng/min/kg).(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
[Maternal serum alpha fetoprotein: the implications for embryofetal status].
Explore the source record for details and available documents.
Adult↗
Prenatal haloperidol alters the expression of DNA polymerases in brain regions of neonate rats.
1. Previous studies have reported a marked reduction in the [3H]thymidine incorporation in forebrain after administration of a dopamine antagonist such as haloperidol. 2. We have investigated the possibility that the expression levels of genes related to DNA metabolism could be altered by haloperidol treatment. 3. By Northern blot analysis, we have studied the steady-state mRNA levels for genes involved in DNA metabolism, in neonate rat mesencephalon and forebrain, after chronic prenatal blockade of dopamine receptors with haloperidol. 4. We found that the expression levels for DNA polymerases alpha and beta were clearly reduced in forebrain by haloperidol treatment. On the contrary, the expression of DNA polymerase beta was increased in mesencephalon. 5. Our results suggest that dopamine receptors occupancy may be a critical factor in controlling cell proliferation during brain development, through a mechanism(s) involving changes in the expression of DNA polymerases.
Animals↗
Eosinophilic proctitis with giant cells: a manifestation of cow's milk protein intolerance.
Two infants, subsequently shown to have cow's milk protein intolerance, presented with rectal bleeding in the first week of life. Rectal biopsies showed eosinophilic infiltration of the mucosa with several multinucleated giant cells. IgG, IgM, and IgA containing plasma cells were present but IgE could not be detected in rectal biopsies. While cow's milk protein intolerance is a well-recognized cause of proctocolitis in infancy, eosinophilic granulomatous-like lesions with giant cells may be a prominent feature and do not exclude the diagnosis.
Biopsy↗
Malignant external otitis and mastoiditis associated with an IgG4 subclass deficiency in a child.
We have presented the first child in Delaware with malignant external otitis associated with IgG4 deficiency. Our patient needed three courses of intravenous antibiotics and twice required mastoidectomy, but has recovered completely following the restoration of the natural barrier between the internal and external ear, using a fascial graft from the large temporalis muscle. Some hearing deficit remains.
Child, Preschool↗
Frequent activation of non-ras transforming sequences in neoplastic Syrian hamster cells initiated with chemical carcinogens.
Carcinogen-caused transformation of Syrian hamster embryo cells has been widely used as a model for experimental carcinogenesis. However, analysis of the molecular mechanisms of hamster cell transformation has been limited. To expand the understanding of the molecular basis of this system, 22 independently derived Syrian hamster neoplastic cell lines initiated with chemical carcinogens were screened for the presence of dominant transforming sequences by DNA transfection into mouse NIH3T3 cells. High molecular weight DNAs from 12 (55%) of these cell lines transformed NIH3T3 cells through serial transfection cycles. NIH3T3 transformants contained hamster-specific repetitive sequences, which co-segregated with the transformed phenotype in successive transfection rounds. Results from Southern hybridization analyses and p21ras mobility assays indicated the presence of N-ras oncogenes, presumably activated by point mutations at codon 61, in 3 of the 12 (25%) transfection positive lines, all initiated with sodium bisulfite; non-ras transforming sequences were apparently activated in the remaining 9 (75%) lines. DNA prepared from NIH3T3 transformants derived from cell line 81C39 was analysed by Southern hybridization with a battery of 38 probes including non-ras oncogenes known to score as positive in the NIH3T3 assay as well as other retroviral and mammalian oncogenes. Each probe hybridized to DNA fragments showing the mobility characteristic of NIH3T3 protooncogenes, but failed to detect homolog sequences of hamster origin, even under hybridization conditions which allowed their detection in hamster DNA. Results show that ras activation occurs at a low frequency in hamster neoplastic transformation and strongly suggest that novel transforming sequences are activated, thus validating the use of this system for investigating the role of non-ras transforming sequences in neoplasia.
Animals↗
Endosonography in the localization of parathyroid tumors: a preliminary study.
A preoperative transesophageal exploration of the parathyroids by endosonography was performed on 23 patients with primary hyperparathyroidism. The system used was a 7.5 MHz transducer mounted on the tip of an endoscope with an external diameter of 13 mm. The field of visualization was 360 degrees. A retrograde exploration was done moving up from the aortic arch to the upper esophageal sphincter. All patients underwent surgery afterward, and adenomas were found. In 12 cases the adenoma was visualized. All 12 adenomas were posteriorly located on the right side (four cases) and left side (eight cases) of the esophagus. Nine of these 12 tumors were on the posterior face of the thyroid lobes, with six tumors in the middle one third of the thyroid lobe and three in the lower one third of the thyroid lobe. The other three tumors were located below the lower pole of the thyroid lobes in the upper posterior mediastinum. Mean tumor weight was 1165 mg. Of the 11 tumors that could not be visualized, eight tumors were anteriorly located; three of these tumors were on the anterior and lateral surface of the lower pole of the thyroid, and five were in the thyrothymic tracts. The remaining three tumors were located on the back of the thyroid lobes; two of these tumors were at the upper esophageal sphincter, and one was on the side of the pharynx. Mean tumor size was 1334 mg. Localization of parathyroid tumors by endosonography appears possible but only if lesions are located posteriorly, close to the esophagus. Endosonography is not indicated before routine cervical exploration for primary or secondary hyperparathyroidism. As in other such studies, endosonography could be useful in cases of persistent or recurrent hyperparathyroidism.
Adenoma↗
Detection by enzymatic amplification of bcr-abl mRNA in peripheral blood and bone marrow cells of patients with chronic myelogenous leukemia.
The Philadelphia chromosome of chronic myelogenous leukemia (CML) patients is caused by a translocation of the c-abl gene from chromosome 9 to the breakpoint cluster region (bcr) on chromosome 22. A new bcr-abl mRNA is expressed in these cases. We have developed a modified polymerase chain reaction (PCR) for the detection of this mRNA. The method is extremely sensitive, reliable, and relatively fast. The analysis of peripheral blood or bone marrow cells from CML patients treated with chemotherapy shows that the two possible mRNAs are expressed in various combinations. Our results show that even after myeloablative therapy for bone marrow transplantation bcr-abl mRNAs are still expressed. Further studies, however, are necessary to determine the clinical relevance of a small number of persisting cells expressing the bcr-abl mRNA.
Blood Cells↗
Ovine fetal lung fluid response to atrial natriuretic factor.
The fetal lung is an important site of fluid production and is postulated to serve a regulatory role in fetal fluid balance. To assess the role of atrial natriuretic factor on fetal lung liquid production, we studied the effect of intravenous atrial natriuretic factor infusion on tracheal fluid production in fetal sheep with chronic vascular and tracheal catheters. Ovine fetuses (mean gestation = 130 days +/- 1 day) received successive 40-minute intravenous infusions of increasing doses of synthetic fragment 1-28 atrial natriuretic factor (5, 25, and 100 ng/min.kg-1). In response to the 25 ng/min.kg-1 infusion, fetal tracheal fluid production decreased from 1.2 +/- 0.3 ml/10 min to 0.6 +/- 0.2 ml/10 min (p less than 0.05), and remained suppressed during the 100 ng/min.kg-1 infusion (0.5 +/- 0.2 ml/10 min). There was a significant inverse correlation between tracheal fluid production and fetal plasma atrial natriuretic factor levels (r = -0.61, p less than 0.001). Basal tracheal fluid sodium and potassium concentrations (147 +/- 1 mEq/L and 5 +/- 1 mEq/L) and osmolality (291 +/- 3 mOsm) did not change during the atrial natriuretic factor infusion periods. The observation that atrial natriuretic factor acts to decrease fetal lung fluid production suggests that atrial natriuretic factor may be important in the fetal adaptive response to extrauterine life.
Animals↗