Prenatal treatment of congenital adrenal hyperplasia.

Prenatal diagnosis of congenital adrenal hyperplasia (CAH) is accurate and prenatal therapy is effective in significantly reducing or even eliminating virilization of females affected by CAH, sparing these children the consequences of genital surgery, sex missassignment and gender confusion. However, both the physical and psychological development of these children and the possibility of long-range adverse effects in the mothers need to be evaluated further. Prospective multicentre studies covering several decades are being designed.     

Influence of a Methanogenic Flora on the Breath H2 and Symptom Response to Ingestion of Sorbitol or Oat Fiber

Background and Objectives: We investigated the possibility that a variant of the normal colonic flora, a high concentration of methanogeas, influences the host's response to ingestion of nonabsorbable, fermentable materials. Methods: To better evaluate symptomatic and breath H₂ and methane (CH₄) responses, subjects were placed on a basal diet (primarily rice and hamburger) that contained minimal amounts of nonabsorbable, fermentable substrate. A breath CH₄/H₂ ratio of greater or less than 1 on the second day of the basal diet was used to categorize subjects as high (N = 9) or low (N = 25) CH₄ producers. After stabilization of the breath gas excretion (day 3 or 4 on the basal diet), the subjects ingested either sorbitol (8.8 g) or oat fiber (10.2 g). Results: The low CH₄ producers had a signficantly higher ( p < 0.05) breath H₂ concentration than the high producers on the basal diet and after ingestion of sorbitol (27.1 ± 2.7 ppm vs 15.8 ± 3.6 ppm) or oat fiber (13.1 ± 0.08 ppm vs 9.6 ± 1.2 ppm). Low producers of methane reported significantly increased bloating and cramping after sorbitol ingestion and increased bloating after fiber ingestion, whereas high CH₄ producers reported no signficant increase in these symptoms. Conclusion: The presence of a methanogenic flora is associated with a reduced symptomatic response to ingestion of nonabsorbable, fermentable material in healthy subjects. Manipulation of the normal flora could be of therapeutic value in nonmethanogenic patients with irritable bowel syndrome.     

Effect of reduced myristoylated alanine-rich C kinase substrate expression on hippocampal mossy fiber development and spatial learning in mutant mice: Transgenic rescue and interactions with gene background

The myristoylated alanine-rich C kinase substrate (MARCKS) is a prominent protein kinase C (PKC) substrate in brain that is expressed highly in hippocampal granule cells and their axons, the mossy fibers. Here, we examined hippocampal infrapyramidal mossy fiber (IP-MF) limb length and spatial learning in heterozygous Macs mutant mice that exhibit an ≈50% reduction in MARCKS expression relative to wild-type controls. On a 129B6(N3) background, the Macs mutation produced IP-MF hyperplasia, a significant increase in hippocampal PKC expression, and proficient spatial learning relative to wild-type controls. However, wild-type 129B6(N3) mice exhibited phenotypic characteristics resembling inbred 129Sv mice, including IP-MF hypoplasia relative to inbred C57BL/6J mice and impaired spatial-reversal learning, suggesting a significant contribution of 129Sv background genes to wild-type and possibly mutant phenotypes. Indeed, when these mice were backcrossed with inbred C57BL/6J mice for nine generations to reduce 129Sv background genes, the Macs mutation did not effect IP-MF length or hippocampal PKC expression and impaired spatial learning relative to wild-type controls, which now showed proficient spatial learning. Moreover, in a different strain (B6SJL(N1), the Macs mutation also produced a significant impairment in spatial learning that was reversed by transgenic expression of MARCKS. Collectively, these data indicate that the heterozygous Macs mutation modifies the expression of linked 129Sv gene(s), affecting hippocampal mossy fiber development and spatial learning performance, and that MARCKS plays a significant role in spatial learning processes.     

Pharmacokinetic study of beta-lactam antibiotics in bronchial secretions.

The objective of the study was to evaluate the concentrations obtained in serum and bronchial secretions after administration of five beta-lactam antibiotics: cephradin (1 g per os) and cefoxitin (2 g i.v. infusion), amoxycillin (1.0 g per os), bacampicillin (0.4 g and 0.8 g per os) and ampicillin (1.0 g per os). 123 adult patients were included in the study and received a single dose of the tested drug. Serum and mucus samples were collected simultaneously 30 minutes, 1, 2 or 4 hours after administration of the drugs. Mucus samples were taken by fibroscopy but in some patients the samples were collected through a tracheostomy cannula which allowed sampling at different time intervals. The results show that the concentrations of penicillins in bronchial secretions increase progressively between one and four hours after administration of the drugs. Bronchial levels obtained after oral administration of ampicillin are low, not more than 5 to 10% of serum levels. The other antibiotics tested show worthwhile concentrations in bronchial secretions, especially with cephalosporins and bacampicillin which exhibits higher serum and bronchial concentrations than ampicillin.     

Evolution of parasitism: kinetoplastid protozoan history reconstructed from mitochondrial rRNA gene sequences.

A phylogenetic tree for the evolution of five representative species from four genera of kinetoplastid protozoa was constructed from comparison of the mitochondrial 9S and 12S rRNA gene sequences and application of both parsimony and evolutionary parsimony algorithms. In the rooted version of the tree, the monogenetic species Crithidia fasciculata is the most deeply rooted, followed by another monogenetic species, Leptomonas sp. The three digenetic species Trypanosoma cruzi, Trypanosoma brucei, and Leishmania tarentolae branch from the Leptomonas line. The substitution rates for the T. brucei and T. cruzi sequences were 3-4 times greater than that of the L. tarentolae sequences. This phylogenetic tree is consistent with our cladistic analysis of the biological evidence including life cycles for these five species. A tentative time scale can be assigned to the nodes of this tree by assuming that the common ancestor of the digenetic parasites predated the separation of South America and Africa and postdated the first fossil appearance of its host (inferred by parsimony analysis). This time scale predicts that the deepest node occurred at 264 +/- 51 million years ago, at a time commensurate with the fossil origins of the Hemiptera insect host. This implies that the ancestral kinetoplastid and its insect host appeared at approximately the same time. The molecular data suggest that these eukaryotic parasites have an evolutionary history that extends back to the origin of their insect host.     

Changes in the isoenzyme and kinetoplast DNA patterns of Trypanosoma cruzi strains induced by maintenance in mice

Culture forms of thirteen Trypanosoma cruzi strains from 4 zymodemes and 9 schizodemes were inoculated and kept by successive passages in C3H mice. The strains were initially from the following zymodemes: 3 from A, 3 from B, 4 from C and 2 from D and 1 from AB mixed zymodemes. After approximately 18 months maintenance the parasites were isolated by hemoculture and again typed according to their isoenzyme and kinetoplast DNA patterns. The zymodeme A strains kept their initial patterns; from the 3 zymodeme B strains, two kept the initial patterns and one changed to zymodeme A; from the 4 zymodeme C, two kept the initial pattern and two changed to zymodeme B; from the 2 zymodeme D strains, one kept the initial pattern and one changed to zymodeme A. The strain from AB mixed zymodeme was reduced to zymodeme. A. The zymodeme changes were accompanied by schizodeme changes. Although not simultaneously, in one T. cruzi strain the parasitemia change was followed by zymodeme and schizodeme changes. The results showed that prolonged maintenance of T. cruzi in mice by successive passages alters the isoenzyme and k-DNA patterns of some strains and that these alterations tend to move towards zymodeme A, suggesting a selective effect of mice over these T. cruzi populations.     

Traumatic lesions of the rectum

Twenty-two patients treated for rectal trauma between 1975 and 1985 were reviewed. There were 13 males and nine females, of mean age 38 years (18–72 years). Causes included gunshot (2), sexual trauma (8), road accident (5), impalement (5), polypectomy (2). Two patients died, giving a treatment mortality of 9%. Cases with peritonitis or sphincter injury were treated by defunctioning colostomy and immediate repair of rectum and sphincter. Of 14 such patients the colostomy had been closed in all but one, who accounted for the only failed sphincter repair out of eight performed. The results show the success of a policy of faecal diversion for intraperitoneal rectal injury and sphincter damage and of local repair without diversion for most cases with extraperitoneal rectal injury.     

Prostaglandin E(1) protects human liver sinusoidal endothelial cell from apoptosis induced by hypoxia reoxygenation

Hepatic ischemia-reperfusion injury is an important cause of graft dysfunction after liver transplantation. Liver sinusoidal endothelial cells (LSECs) are particularly sensitive to ischemia-reperfusion injury and undergo apoptosis. This study investigates the protective role of PGE(1) on apoptosis of LSEC during hypoxia-reoxygenation in vitro. Hypothermia-hypoxia followed by reoxygenation triggered LSEC apoptosis, and prostaglandin PGE(1) protected LSEC from apoptosis in a dose-dependent manner. The release of matrix metalloproteinases (MMPs) and nitric oxide (NO) by LSECs were increased after hypoxia reoxygenation. Both the MMP inhibitor BB3103 and the NO inhibitor LNAM effectively decreased LSEC apoptosis, suggesting a separate role of MMPs and NO in hypoxia-reoxygenation-induced LSEC apoptosis. PGE(1) down-regulated NO production by inhibiting the expression of inducible NO synthase in LSEC. PGE(1) also inhibited MMP-2 release from LSEC during hypoxia reoxygenation. These results indicate that the protection of LSECs from apoptosis by PGE(1) in hepatic ischemia-reperfusion injury is mediated by inhibiting inducible NO synthase and MMP release.     

Ultrastructural evidence for endogenous somatostatin-like immunoreactivity in the pituitary gland

The tetradecapeptide, somatostatin (SRIF), is a potent inhibitor on pituitary hormone release, by a direct effect. The immunocytological method was used with the aim of localizing SRIF at the cellular and subcellular levels. Rat pituitaries were fixed and frozen. Ultrathin sections obtained by cryoultramicrotomy, were incubated with anti-SRIF serum. The antigen-antibody reaction was detected by 4-chloro-1-naphthol. SRIF immunoreactivity was observed in somatotrophs, thyreotrophs and prolactin cells, but not in corticotrophs or gonadotrophs. Im immunoreactive cells, SRIF was found in the cytoplasmic matrix, in the secretory granules and in the nucleus distributed primarily in the euchromatin, in the vicinity of the heterochromatin regions. SRIF immunoreactivity was also observed at the plasma membrane. No immunoreactivity was observed when nonimmune serum or anti-SRIF serum incubated with SRIF was used. No modification was observed when anti-SRIF serum incubated with gonadoliberin, thyroliberin or vasopressin was used. These data (1) provide immunocytological evidence for the presence of somatostatin in pituitary gland, and (2) indicate the presence of SRIF peptide in the somatotrophs, thyreotrophs and prolactin cells.