piperidines and Bacterial-Infections

The pipeline for new antibacterials is bleak despite the fact that infectious diseases account for a quarter of all worldwide deaths due to disease. Bacteria are ideal organisms for a systems biology approach to understanding pathogenesis by combined use of genomic technologies and computer algorithms. This approach can be applied to identify control points in molecular networks, which could be targets for novel drugs.

Topics: Alkaloids; Animals; Anti-Bacterial Agents; Bacterial Infections; Benzodioxoles; Drug Design; Genome, Bacterial; Humans; Piperidines; Polyunsaturated Alkamides; Systems Biology

One hundred and twelve patients with acute infectious diarrhoea were entered in a double-blind randomised study in order to compare loperamide with a placebo. Of 82 evaluable patients, 38 received loperamide and 44 placebo for a maximum of 5 days. There were no significant differences in the number of loose stools during the first day of treatment, in the total number of tablets taken or in the total duration of the period of diarrhoea between the two treatment groups. The loperamide-treated patients had significantly fewer loose stools during the observation period of 5 days than did the placebo treated patients, median five vs. seven, a difference of little clinical importance. Excretion of bacterial pathogens was followed weekly in 13 of the loperamide treated patients (median 35.5 days) and in 18 of the placebo treated patients (median 22.5 days). This difference in the duration of excretion was not significant.

Topics: Acute Disease; Adolescent; Adult; Aged; Bacterial Infections; Clinical Trials as Topic; Diarrhea; Double-Blind Method; Female; Humans; Loperamide; Male; Middle Aged; Piperidines; Time Factors

Plant bacterial diseases are an intractable problem due to the fact that phytopathogens have acquired strong resistances for traditional pesticides, resulting in restricting the quality and yield of agricultural products around the world. To develop new agrochemical alternatives, we prepared a novel series of sulfanilamide derivatives containing piperidine fragments and assessed their antibacterial potency. The bioassay results revealed that most molecules displayed excellent in vitro antibacterial potency towards

Topics: Anti-Bacterial Agents; Bacterial Infections; Dihydropteroate Synthase; Microbial Sensitivity Tests; Oryza; Oxadiazoles; Piperidines; Plant Diseases; Sulfanilamide; Sulfonamides; Xanthomonas

We describe the opportunistic infections occurring in 362 patients with lymphoproliferative disorders treated with ibrutinib and idelalisib in clinical practice. Overall, 108 of 362 patients (29·8%) developed infections, for a total of 152 events. Clinically defined infections (CDI) were 49·3% (75/152) and microbiologically defined infections (MDI) were 50·7% (77/152). Among 250 patients treated with ibrutinib, 28·8% (72/250) experienced one or more infections, for a total of 104 episodes. MDI were 49% (51/104). Bacterial infections were 66·7% (34/51), viral 19·6% (10/51) and invasive fungal diseases (IFD) 13·7% (7/51). Among the 112 patients treated with idelalisib, 32·1% (36/112) experienced one or more infections, for a total of 48 episodes. MDI were 54·2% (26/48). Bacterial infections were 34·6% (9/26), viral 61·5% (16/26) and IFD 3·8% (1/26). With ibrutinib, the rate of bacterial infections was significantly higher compared to idelalisib (66·7% vs. 34·6%; P = 0·007), while viral infections were most frequent in idelalisib (61·5% vs. 19·6%; P < 0·001). Although a higher rate of IFD was observed in patients treated with ibrutinib, the difference was not statistically significant (13·7% vs. 3·8% respectively; P = 0·18). Bacteria are the most frequent infections with ibrutinib, while viruses are most frequently involved with idelalisib.

Topics: Adenine; Agammaglobulinaemia Tyrosine Kinase; Aged; Aged, 80 and over; Bacterial Infections; Case-Control Studies; Enzyme Inhibitors; Female; Humans; Invasive Fungal Infections; Italy; Lymphoproliferative Disorders; Male; Middle Aged; Molecular Targeted Therapy; Opportunistic Infections; Piperidines; Protein Kinase Inhibitors; Purines; Quinazolinones; Retrospective Studies; Risk Factors; Virus Diseases

Topics: Adenine; Agammaglobulinemia; Aged; Bacterial Infections; Humans; Immunoglobulins; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Piperidines; Pyrazoles; Pyrimidines; Recurrence; Sinusitis

Ibrutinib is a Bruton tyrosine kinase inhibitor that is used for the treatment of lymphoid cancers, including chronic lymphocytic leukemia, Waldenström macroglobulinemia, and mantle cell lymphoma. Several case series have described opportunistic infections among ibrutinib recipients, but the full extent of these infections is unknown. We sought to determine the spectrum of serious infections associated with ibrutinib treatment.. We reviewed the electronic medical records of patients with lymphoid cancer at Memorial Sloan Kettering Cancer Center who received ibrutinib during a 5-year period from 1 January 2012 to 31 December 2016. Serious infections were identified by review of the relevant microbiology, clinical laboratory, and radiology data. Risk factors for infection were determined by means of univariate and multivariate analyses.. We analyzed findings in 378 patients with lymphoid cancer who received ibrutinib. The most common underlying cancers were chronic lymphocytic leukemia and mantle cell lymphoma. 84% of patients received ibrutinib as monotherapy. Serious infection developed in 43 patients (11.4%), primarily during the first year of ibrutinib treatment. Invasive bacterial infections developed in 23 (53.5%) of these patients, and invasive fungal infections (IFIs) in 16 (37.2%) .The majority of patients with IFIs during ibrutinib therapy (62.5%) lacked classic clinical risk factors for fungal infection (ie, neutropenia, lymphopenia, and receipt of corticosteroids). Infection resulted in death in 6 of the 43 patients (14%).. Patients with lymphoid cancer receiving ibrutinib treatment are at risk for serious infections, including IFIs.

Topics: Adenine; Adult; Aged; Aged, 80 and over; Bacterial Infections; Electronic Health Records; Female; Humans; Invasive Fungal Infections; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Mantle-Cell; Lymphopenia; Male; Middle Aged; New York; Opportunistic Infections; Piperidines; Pyrazoles; Pyrimidines; Risk Factors; Young Adult

Sedating and non-sedating histamine H(1) receptor (H1R) antagonists and H2R blockers are widely used drugs which are generally considered to be safe medications. However, recently, these drugs have been shown to possibly impair the outcome of perforating appendicitis in children.. It was the aim of this study to characterize the effects of histamine receptor blockade in severe bacterial infections in more detail.. To obtain information on the safety of histamine receptor blockade in more detail, we used pharmacological and genetic approaches targeting histamine receptors and performed cecal ligation and puncture (CLP), a mouse model of septic peritonitis. After induction of septic peritonitis, morbidity and mortality were monitored closely.. Here, we show that oral treatment with first-generation H1R antihistamine diphenhydramine, H2R blocker cimetidine and H3/4R blocker thioperamide impairs optimal innate immune responses in severe murine bacterial sepsis. However, these adverse effects are not mediated by H1R, as mice deficient for H1R show similar rates of morbidity and mortality after CLP as their wild-type controls. Similarly, the second-generation antihistamine desloratadine neither affects morbidity nor mortality after CLP.. Our findings indicate that sedating first-generation H1R antihistamines and H2R blockers might impair innate immune responses to bacteria and that these drugs should be used with caution in patients with severe bacterial infections.

Topics: Animals; Anti-Allergic Agents; Bacterial Infections; Diphenhydramine; Histamine Antagonists; Histamine H1 Antagonists; Histamine H1 Antagonists, Non-Sedating; Histamine H3 Antagonists; Humans; Immunity, Innate; Loratadine; Mice; Mice, Inbred C57BL; Peritonitis; Piperidines; Receptors, Histamine; Sepsis

The objective of this study was to investigate the human teratogenic potential of oral prenoxdiazine treatment during pregnancy. The analysis of cases with congenital abnormalities and their matched controls without congenital abnormalities was performed in the large population-based data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996. Of the 22,843 pregnant women who had offspring with congenital abnormalities, 158 (0.7%) were treated with prenoxdiazine. Of the 38,151 pregnant women who had babies without any defects in the study period (control group), 226 (0.6%) were treated with prenoxdiazine (adjusted prevalence odds ratio, 1.0; 95% confidence interval, 0.8-1.3). The comparison of cases and their matched controls did not show a significantly higher rate of prenoxdiazine treatment during the second and third months of gestation in the total (adjusted prevalence odds ratio, 1.4; 95% confidence interval, 0.9-2.2) or in any group of congenital abnormalities. Treatment with prenoxdiazine during pregnancy did not have any teratogenic risk to the fetus. Thus, prenoxdiazine treatment in pregnant women with an unproductive cough may be beneficial.

Topics: Abnormalities, Drug-Induced; Administration, Oral; Adult; Bacterial Infections; Case-Control Studies; Female; Humans; Hungary; Piperidines; Pregnancy; Pregnancy Complications; Pregnancy Trimester, Second; Pregnancy Trimester, Third

We have reported that injection of marijuana cannabinoids, such as Delta(9)-tetrahydrocannabinol (THC), into mice, followed by infection with Legionella pneumophila (Lp), suppresses the development of cell-mediated immunity T helper 1 (Th1) activity. These effects are accompanied by suppression of interleukin (IL)-12 and interferon (IFN) gamma production and enhancement of IL-4 production suggesting THC-induced T helper cell biasing. In the current report, other T helper cell biasing mechanisms were studied. Mice were injected with THC followed 18 h later by a challenge infection with Lp. Two-hour post-infection, spleens were removed and analyzed for mRNA to either IL-12Rbeta2 or GATA3 gene products. The results showed that THC suppressed IL-12Rbeta2 but increased GATA3. Receptor antagonists for CB1 (SR141716A, SR1) and CB2 (SR144528, SR2) were also injected to analyze the involvement of cannabinoid receptors. It was determined that SR1 attenuated the THC suppression of IL-12Rbeta2, while SR2 attenuated the increase in GATA3 mRNA. These results suggest that THC suppresses Th1 biasing activity such as IL-12Rbeta2 by a CB1 mediated mechanism and enhances the Th2 biasing activity, GATA3, by a CB2 mechanism. This dichotomy of receptor involvement might result from differential expression and/or signaling function of CB1 and CB2 on Th1 and Th2 cells.

Topics: Animals; Bacterial Infections; Camphanes; Cannabinoid Receptor Antagonists; Cells, Cultured; DNA-Binding Proteins; Dronabinol; Drug Interactions; GATA3 Transcription Factor; Interferon-gamma; Interleukin-2; Interleukin-2 Receptor beta Subunit; Legionella pneumophila; Mice; Piperidines; Psychotropic Drugs; Pyrazoles; Receptors, Cannabinoid; Receptors, Interleukin; Reverse Transcriptase Polymerase Chain Reaction; Rimonabant; RNA, Messenger; Signal Transduction; Spleen; T-Lymphocytes, Helper-Inducer; Th2 Cells; Trans-Activators

The discovery of a potent intracellular inhibitor of human neutrophil elastase which is orally active and has a long duration of action is described. The pharmacodynamic and pharmacokinetic properties of a trans-lactam development candidate, GW311616A, are described.

Topics: Administration, Oral; Animals; Bacteria; Bacterial Infections; Biological Availability; Cricetinae; Crystallization; Dogs; Drug Stability; Lactams; Leukocyte Elastase; Metabolic Clearance Rate; Pancreatic Elastase; Piperidines; Rats; Serine Endopeptidases; Serpins

A possible role of platelet-activating factor (PAF) in the occurrence of the two septic complications, i.e., disseminated intravascular coagulation (DIC) and multiple organ failure (MOF) was investigated, employing a rabbit model and a novel PAF antagonist E5880. By an instillation of fecal suspension into the common bile duct of the rabbit, manifestations of DIC and MOF were observed with high reproducibility by 9 hours after the septic insult. E5880 was intravenously administered to 12 rabbits for 1 hour after the septic insult at dose of 1 mg/kg (n = 6) or 3mg/kg (n = 6). All the rabbits were subjected to observation of vital signs and serial determination of laboratory tests for 9 hours and then lung, liver and kidney were removed for histological examination. Blood endotoxin level increased significantly by 9 hours after the septic insult. Although administration of E5880 did not affect the endotoxemia, the antagonist attenuated in a dose related manner laboratory manifestation of DIC such as thrombocytopenia and prolonged prothrombin time as well as that of MOF such as increase in serum bilirubin and creatinine level. The beneficial effect of E5880 on MOF was also confirmed by the histological evaluation. These observations indicated that PAF is deeply involved in the occurrence of DIC and MOF due to sepsis and E5880 may be one of the modalities to treat or prevent these two major septic complications.

Topics: Alanine Transaminase; Animals; Bacterial Infections; Blood Cell Count; Blood Urea Nitrogen; Cholangitis; Common Bile Duct; Disseminated Intravascular Coagulation; Endotoxins; Fibrinogen; Hematocrit; Liver; Male; Multiple Organ Failure; Partial Thromboplastin Time; Piperidines; Platelet Activating Factor; Pyridinium Compounds; Rabbits

Topics: Adult; Animals; Bacterial Infections; Child; Diarrhea; Humans; Loperamide; Piperidines; Rats

The result of our examinations was that instillagel has a desinfecting effect in the urethra. This result is mathematically secured by means of the 2 I-test and highly significant. 95% of the preoperatively infected urethras were germ-free immediately after operation. This effect could not be proved in nifucin-gel-medicain as well as in urocomb. Using these lubricants all preoperatively infected urethras were also infected immediately after operation.

Topics: Anti-Infective Agents, Urinary; Bacterial Infections; Chlorhexidine; Drug Combinations; Electrosurgery; Humans; Lidocaine; Lubrication; Male; Nitrofurazone; Piperidines; Postoperative Complications; Propiophenones; Prostatic Hyperplasia; Prostatic Neoplasms; Tetracaine; Urethra; Urinary Bladder Neoplasms; Urinary Tract Infections

Topics: Acute Disease; Bacterial Infections; Butyrates; Child; Child, Preschool; Diarrhea, Infantile; Enteritis; Gastroenteritis; Gastrointestinal Agents; Humans; Infant; Infant, Newborn; Piperidines; Virus Diseases