A double-blind comparative multicentre study of controlled-release remoxipride, immediate-release remoxipride and haloperidol in schizophrenia.

A double-blind multicentre study comparing the efficacy and safety of remoxipride in controlled-release formulation (REM-CR), given once a day, and immediate-release formulation (REM-IR) and haloperidol, given twice daily, was conducted in patients with schizophrenic illness. In total, 150 inpatients were randomized: 49, 51 and 50 in the REM-CR, REM-IR, and haloperidol groups, respectively. The mean daily dose of REM-CR during the last week of treatment was 361 mg, that of REM-IR 332 mg. In the haloperidol group the corresponding dose was 12.5mg per day. The study treatment period was four weeks. The median BPRS total score was 37.5 in the REM-CR group at start of treatment, and 14.5 at last rating (n = 38). For the REM-IR group and the haloperidol group the corresponding figures were 36.0 and 38.0 at start of treatment and 18.0 (n = 43) and 16.5 (n = 40) at last rating. No statistically significant differences were found between the treatments. Therapy-emergent extrapyramidal symptoms (Simpson & Angus rating scale) were significantly (p less than 0.05) more frequent and more severe during haloperidol than during REM-CR and REM-IR treatment, despite significantly higher concurrent use of anticholinergic drugs in the haloperidol group.--REM-CR was comparable in efficacy and tolerability to REM-IR. The tolerability profile favoured both remoxipride formulations over haloperidol. Evaluation of the clinical chemistry, haematology, and cardiovascular data showed no clinically significant deleterious effects on any organ system for either drug.     

In vivo colonization of the mouse large intestine and in vitro penetration of intestinal mucus by an avirulent smooth strain of Salmonella typhimurium and its lipopolysaccharide-deficient mutant.

The relative abilities of an avirulent Salmonella typhimurium strain with wild-type lipopolysaccharide (LPS) character, SL5319, and a nearly isogenic LPS-deficient mutant, SL5325, to colonize the large intestines of streptomycin-treated CD-1 mice in vivo and to penetrate colonic mucus in vitro were studied. Previously it had been shown that, when fed simultaneously to streptomycin-treated mice (approximately 10(10) CFU each), the S. typhimurium strain with wild-type LPS colonized at 10(8) CFU/g of feces indefinitely, whereas the LPS-deficient mutant dropped within 3 days to a level of only 10(4) CFU/g of feces. In the present investigation, when SL5325 was allowed to colonize for 8 days before feeding mice SL5319 or when it was fed to mice simultaneously with an Escherichia coli strain of human fecal origin (10(10) CFU each), both strains colonized indefinitely at 10(7) CFU/g of feces. Moreover, when the wild-type and LPS-deficient mutant strains were fed to mice simultaneously in low numbers (approximately 10(5) CFU each) the strains survived equally well in the large intestines for 8 days, after which the LPS-deficient mutant was eliminated (less than 10(2) CFU/g of feces), whereas the wild-type colonized at a level of 10(7) CFU/g of feces. In addition although both strains were able to adhere to mucus and epithelial cell preparations in vitro, the wild-type strain was shown to have greater motility and chemotactic activity on CD-1 mouse colonic mucus in vitro and to more rapidly penetrate and form a stable association with immobilized colonic mucosal components in vitro. Based on these data, we suggest that the ability of an S. typhimurium strain to colonize the streptomycin-treated mouse large intestine may, in part, depend on its ability to penetrate deeply into the mucus layer on the intestinal wall and subsequently, through growth, colonize the mucosa.     

Identification of two new HLA alleles: B*3546* and B*5611*. How reliable are the published HLA-B intron 2 sequences?

Polymerase chain reaction-sequence-specific primer (PCR-SSP) typing for human leukocyte antigen (HLA)-B in a male 25-year-old Caucasian individual of Iranian origin and in a 42-year-old German Caucasian bone marrow donor revealed reaction patterns that did not agree with any known HLA specificity, thus suggesting in both cases the existence of a novel allele. Sequence-based typing (SBT) after allelic separation revealed the sequences of the new alleles HLA-B*5611 and B*3546. The sequence patterns of both new alleles might have been generated as the results of double crossing over, possibly over several generations. During the analysis of the HLA-B*3546 intron 2 sequence for possible crossing over points, a base insert, an additional G after position 700, was found. This insert was analyzed using SBT and PCR-SSP and was found to be present not only in all samples carrying B*35, but also in all HLA-B specificities tested. It appears that all known HLA-B alleles may contain a G insert at position 700 of intron 2, and that the published intron 2 sequence alignments of the HLA-B locus may contain errors at this position.     

Escherichia coli F-18 and E. coli K-12 eda mutants do not colonize the streptomycin-treated mouse large intestine.

The Escherichia coli human fecal isolates F-18 and K-12 are excellent colonizers of the streptomycin-treated mouse intestine. E. coli F-18 and E. coli K-12 eda mutants (unable to utilize glucuronate, galacturonate, and gluconate) were constructed by insertional mutagenesis. Neither the E. coli F-18 eda nor the E. coli K-12 eda mutant was able to colonize the streptomycin-treated mouse intestine, whether they were fed to mice together with their respective parental strains or alone. Complementation of the eda mutants with pTC190 (containing a functional E. coli K-12 eda gene) completely restored the colonization ability of both eda mutants. Relative to their parental strains, the E. coli F-18 eda mutant and the E. coli K-12 eda mutant grew poorly in cecal mucus isolated from mice fed either normal mouse chow or a synthetic diet containing sucrose as the sole carbon source, yet the mutants and parental strains demonstrated identical growth rates in minimal medium with glucose as the carbon source. E. coli F-18 edd eda and E. coli K-12 edd eda double mutants colonized the streptomycin-treated intestine when fed to mice alone; however, when fed simultaneously with their respective parental strains, they were poor colonizers. Since the edd gene is involved only in gluconate metabolism via the Entner-Doudoroff pathway, these results implicate the utilization of gluconate and the Entner-Doudoroff pathway as important elements in E. coli colonization of the streptomycin-treated mouse large intestine.     

Abnormal responsiveness of growth hormone to human corticotropin-releasing hormone in major depressive disorder

Plasma growth hormone (GH) release after injection of 100 micrograms synthetic human corticotropin-releasing hormone (hCRH) was investigated in 11 patients with major depressive disorder and normal controls matched for gender, age, body weight and ovarian status. In contrast to controls, who exhibited no significant GH response to CRH, depressed patients showed a significant net increase in GH secretion following CRH administration. The abnormal GH response to CRH was not correlated with baseline corticotropin (ACTH) and cortisol nor with CRH-induced ACTH and cortisol response. The implications of these findings are discussed with reference to such factors as alpha-adrenergic hyperactivity, hypothalamic-pituitary system dysregulation, drug interference, non-specific stress responses and abnormal neuroendocrine circadian rhythms in major depression.     

Anti-inflammatory activity of hamamelis distillate applied topically to the skin

Summary The anti-inflammatory activity of hamamelis distillate has been evaluated with respect to drug concentration (0.64 mg/2.56 mg hamamelis ketone/100 g) and the effect of the vehicle (O/W emulsion with/without phosphatidylcholine (PC) in an experimental study. The effects were compared with those of chamomile cream, hydrocortisone 1% cream and 4 base preparations. Erythema was induced by UV irradiation and cellophane tape stripping of the horny layer in 24 healthy subjects per test. Skin blanching was quantified by visual scoring and chromametry. Drug effects were compared with one another and with an untreated control area, as well as with any action due to the vehicle.UV-induced erythema at 24 h was suppressed by low dose hamamelis PC-cream and hydrocortisone cream. Hydrocortisone appeared superior to both hamamelis vehicles, hamamelis cream (without PC) and chamomile cream. The latter preparation was also less potent than hamamelis PC-cream. Erythema 4 to 8 h after the stripping of the horny layer was suppressed by hydrocortisone (P0.05). Inflammation was also less pronounced following low dose hamamelis PC-cream and chamomile cream. Hamamelis PC-cream, however, appeared less potent than hydrocortisone. In general, visual scoring was more discriminatory than chromametry.The results have demonstrated an anti-inflammatory activity of hamamelis distillate in a PC-containing vehicle. A fourfold increase of drug concentration, however, did not produce an increase in activity.     

Case Report: A Case of Diabetic Ketoacidosis Following Chikungunya Virus Infection

Chikungunya is a mosquito-borne viral disease that has recently become endemic in the Caribbean, including the island of Puerto Rico. We present the case of a 50-year-old Puerto Rican man who traveled to St. Louis for business and was diagnosed with acute chikungunya virus infection with atypical features causing diabetic ketoacidosis. This case highlights the need to keep tropical infectious diseases on the differential diagnosis in appropriate individuals and the ways in which tropical infectious diseases can masquerade as part of common presentations.     

L-fucose stimulates utilization of D-ribose by Escherichia coli MG1655 DeltafucAO and E. coli Nissle 1917 DeltafucAO mutants in the mouse intestine and in M9 minimal medium

Escherichia coli MG1655 uses several sugars for growth in the mouse intestine. To determine the roles of L-fucose and D-ribose, an E. coli MG1655 DeltafucAO mutant and an E. coli MG1655 DeltarbsK mutant were fed separately to mice along with wild-type E. coli MG1655. The E. coli MG1655 DeltafucAO mutant colonized the intestine at a level 2 orders of magnitude lower than that of the wild type, but the E. coli MG1655 DeltarbsK mutant and the wild type colonized at nearly identical levels. Surprisingly, an E. coli MG1655 DeltafucAO DeltarbsK mutant was eliminated from the intestine by either wild-type E. coli MG1655 or E. coli MG1655 DeltafucAO, suggesting that the DeltafucAO mutant switches to ribose in vivo. Indeed, in vitro growth experiments showed that L-fucose stimulated utilization of D-ribose by the E. coli MG1655 DeltafucAO mutant but not by an E. coli MG1655 DeltafucK mutant. Since the DeltafucK mutant cannot convert L-fuculose to L-fuculose-1-phosphate, whereas the DeltafucAO mutant accumulates L-fuculose-1-phosphate, the data suggest that L-fuculose-1-phosphate stimulates growth on ribose both in the intestine and in vitro. An E. coli Nissle 1917 DeltafucAO mutant, derived from a human probiotic commensal strain, acted in a manner identical to that of E. coli MG1655 DeltafucAO in vivo and in vitro. Furthermore, L-fucose at a concentration too low to support growth stimulated the utilization of ribose by the wild-type E. coli strains in vitro. Collectively, the data suggest that L-fuculose-1-phosphate plays a role in the regulation of ribose usage as a carbon source by E. coli MG1655 and E. coli Nissle 1917 in the mouse intestine.