Topical cyclosporine inhibits mast cell-mediated conjunctivitis

PURPOSE: Allergic conjunctivitis is a common condition caused by a mast cell-mediated hypersensitivity reaction to immunoglobulin E-bound allergens. The purpose of this study was to investigate the effect of topical cyclosporine A on the development of mast cell-mediated conjunctivitis in mice. METHODS: Allergic conjunctivitis was induced in C57BL/6 mice by topical applications of compound 48/80, a mast cell degranulating agent. In two separate experiments, mice were treated with topical cyclosporine A (0.05%, 0.2%, or 0.4%), prednisolone acetate 1%, or phosphate-buffered saline. Twenty-four hours after compound 48/80 instillation, the number of neutrophils, eosinophils, lymphocytes, macrophages, and the number of preserved goblet cells and undegranulated mast cells in the conjunctiva were counted by a masked observer. RESULTS: In both experiments, treatment with all three doses of cyclosporine A resulted in a statistically significant reduction in the number of infiltrating neutrophils and eosinophils compared to saline-treated controls. There was no significant difference in the treatment effect of cyclosporine and prednisolone acetate. In addition, there was increased preservation of goblet cells in the cyclosporine A-treated animals. Immunohistochemical staining showed a reduction in infiltrating lymphocytes and a smaller reduction in infiltrating macrophages in animals treated with cyclosporine compared to saline-treated controls. CONCLUSIONS: Topical cyclosporine A was effective in inhibiting the development of mast cell-mediated allergic conjunctivitis in mice. This study suggests that topical cyclosporine A may be effective in treating allergic conjunctivitis in humans.     

Heat-stabilized albumin microspheres as a sustained drug delivery system for the antimetabolite, 5-fluorouracil

A nested polymerase chain reaction (PCR) test was developed to examine infection with the bovine lentivirus, bovine immunodeficiency-like virus (BIV), in cattle. Primers were designed to amplify 2 separate regions of the pol and env segments of the BIV genome. Two calves were experimentally infected with an isolate derived from the original strain of BIV, R29, or with a recent field isolate, FL491. Serial blood samples were collected and examined by virus isolation, protein immunoblot, and nested PCR. The nested PCR test detected BIV infection by 3 days after inoculation, earlier than the other 2 methods, and continued to identify infected cattle 9 to 15.5 months after inoculation, even when results from virus isolation and serology became negative. Nested PCR also detected multiple-size env products in samples obtained later in the infection from the calf that received FL491, giving evidence that viral quasispecies were selected during in vivo replication of the virus. Results indicated that the nested PCR test is more sensitive than virus isolation or serology for the detection of BIV infection in cattle.     

Psychic hygiene as a possible special discipline

One hundred and twenty healthy Nigerian female patients undergoing minor gynaecological operations were divided randomly into two groups. One group of 58 patients received intramuscular atropine as the only premedication on the ward while the other group of 62 patients received their atropine intravenously at the time of induction of anaesthesia. Anaesthesia was induced with thipentone and maintained with nitrous oxide, oxygen, and halothane using a facemask. There was equally satisfactory control of secretions in both groups. However, due to the occasional difficulties in achieving optimal timing of intramuscular atropine as well as the uncomfortably dry mouth complained of by 87.7 per cent of the patients who had intramuscular atropine, the intravenous administration at induction is to be preferred. Moreover, one saves the patient an extra injection.     

Bioluminescence as a possible auxiliary oxygen detoxifying mechanism in elaterid larvae

An emerging hypothesis considers the process of neuronal apoptosis as a consequence of unscheduled and unsynchronized induction of cell cycle mediators. Induction of several cell cycle genes precedes neuronal apoptosis and may be involved in determination of cell fate. We have now characterized changes in expression of cell cycle genes during apoptosis induced by oxidative stress in chick post-mitotic sympathetic neurons. Induction of cyclin B occurred prior to the commitment of neurons to both dopamine- and peroxide-triggered apoptosis. Both the neuronal death and the rise in cyclin B were inhibited by antioxidant treatment, suggesting a functional role for cyclin B induction during neuronal apoptosis. Induction of the cyclin dependent kinase CDK5 protein coincided with the time point when neurons were irreversibly committed to die. Expression of other cell cycle mediators such as cyclin D1 and the cyclin dependent kinases CDC2 and CDK2 was undetected and not induced by exposure to oxidative stress. Comparative analysis of the profile of cell cycle mediators induced during neuronal apoptosis of different neuronal cell populations revealed no distinct pattern of events. There are no cell cycle stage-specific mediators that are ultimately stimulated during neuronal apoptosis, suggesting that multiple pathways of re-activating the dormant cell-cycle, converge to determine entry into apoptosis. Nevertheless, the existence of some cell cycle mediators, that were not reported so far to be induced in post mitotic neurons during oxidative stress, substantiate them as part of the strong differentiating forces.     

Human herpesvirus 6 as a possible cause of pneumonia

BACKGROUND: In biological studies of periodontitis, there has been long-standing confusion between the ubiquitous phenomena of inflammation and the essential criterion of attachment loss. This is partly attributable to inadequate methods of clinical measurement, but seems also to be a consequence of an unproven and usually unstated assumption that the same biological processes underlie both inflammation and attachment loss. Developments in unidimensional clinical probing methods have helped in studies of periodontal treatment. However, such methods are intrinsically unsuitable in studies of periodontal diseases, and may have given them a false sense of security. the confusion has been compounded by inappropriate use of statistical techniques in an attempt to solve problems which do not arise from mathematical models but are intrinsic to measurement methods. OBJECTIVE: This paper is a clinician's attempt to state the current difficulties and suggest some ways forward, including the development of three-dimensional measurement, non-invasive probing, and several objectives for biochemical, microbiological and immunological research.     

Acetonitrile as a possible marker of current cigarette smoking

Volatile nitriles are present in cigarette smoke. We tested the hypothesis that the presence of any of four nitriles in the blood can serve as a marker of recent cigarette smoking. We determined the sensitivity and specificity of these nitriles as indicators of daily cigarette smoking in 24 smokers (Group A) and 18 non-smokers (Group B), as well as the correlation between intensity of daily smoking and the blood concentration of acetonitrile. A new head space GLC assay method was used. Of the four nitriles, only acetonitrile was present in the blood of any study subject. Acetonitrile was moderately sensitive (67%) and entirely specific (100%) for self-reported daily smoking. There was fair correlation between blood acetonitrile concentration and the average daily number of cigarettes smoked (r2 = 0.39; P = 0.001), and the mean blood acetonitrile concentration was significantly higher (P = 0.03) among subjects with higher (> 10 cigarettes per day) current cigarette exposure (148.3 +/- 18.0 micrograms/l) than among smokers with low or minimal (1-10 cigarettes per day) exposure (43.3 +/- 6.0 micrograms/l). Thus, acetonitrile in blood appears to be highly specific and a moderately sensitive marker of cigarette smoking with a dose-effect relationship. As such, acetonitrile shows promise as a marker of current cigarette exposure.     

Hyperforin as a possible antidepressant component of hypericum extracts

We demonstrate that the phloroglucinol derivative hyperforin is not only the major lipophilic chemical constituent of the medicinal plant Hypericum perforatum (St. John's wort) but also a potent uptake inhibitor of serotonin (5-HT), dopamine (DA), noradrenaline (NA), GABA and L-Glutamate with IC50 values of about 0.05-0.10 microg/ml (5-HT, NA, DA, GABA) and about 0.5 microg/ml (L-glutamate) in synaptosomal preparations. Furthermore, potencies of two different hypericum extracts in two conventional pharmacological paradigms useful for the detection of antidepressants (behavioral despair, learned helplessness), closely correlate with their hyperforin contents. In addition, most till now known neuropharmacological properties of the clinically used hypericum extracts can also be demonstrated with pure hyperforin. It appears, therefore, that this non-nitrogenous constituent is a possible major active principle responsible for the observed clinical efficacies of the extract as an antidepressant and that it could also be a starting point for drug discovery projects engaged in the search of psychoactive drugs with novel mode of action.     

Irreversible cataract as a possible side effect of isoretinoin

BACKGROUND: Isoretinoin, a drug used in the treatment of severe cystic acne, is known for its numerous adverse ocular side effects, among others. Generally these side effects are benign in nature and reversible on cessation of drug therapy, as for instance transient acute myopia. However, two cases of irreversible cataract possibly related to isotretinoin have been described up till now. PATIENT: We examined a 37-year-old woman with acute unilateral cataract that occurred after a treatment with isotretinoin for four months, terminated a few days previously. A clear etiological relation could not be established. CONCLUSION: The time relation, the acute onset and the absence of other factors nevertheless suggest an influence of isotretinoin therapy to the occurrence of the cataract.     

Topical antimicrobials applied to the umbilical cord stump: a new intervention against neonatal tetanus

Primary epididymal malignancies are uncommon, and epididymal adenocarcinomas are exceedingly rare. We report a case of primary adenocarcinoma of the epididymis in a 62-year-old man and review the world literature on epididymal adenocarcinoma.     

Serum hepatocyte growth factor as a possible indicator of arteriosclerosis

OBJECTIVE: To investigate the possible involvement of hepatocyte growth factor in arteriosclerotic lesions, by studying the relationship between serum concentrations of hepatocyte growth factor and grades of retinal arteriosclerosis. METHODS: We measured the blood pressure, body mass index, serum concentrations of total cholesterol, high-density lipoprotein cholesterol, triglycerides, creatinine, uric acid, total protein, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, gamma-glutamyltranspeptidase, alkaline phosphatase, and hepatocyte growth factor, erythrocyte counts, hemoglobin concentration, and hematocrit levels of 112 adults. Serum concentrations of hepatocyte growth factor were measured by a specific enzyme-linked immunosorbent assay. For each subject, photographs of both optic fundi were taken, and the grade of arteriosclerotic changes in the retinal arteries was evaluated according to Scheie's classification. RESULTS: Individuals with more advanced grades of arteriosclerotic changes had higher serum hepatocyte growth factor values (grade 0, 0.056 +/- 0.004 ng/ml, n = 86; grade 1, 0.132 +/- 0.026 ng/ml, n = 17, P < 0.01, versus grade 0; grade 2-3, 0.271 +/- 0.023 ng/ml, n = 9, P < 0.01, versus grades 0 and 1). The serum hepatocyte growth factor concentrations were also correlated significantly to the serum uric acid concentrations (r = 0.230, P = 0.015) and erythrocyte counts (r = 0.299, P = 0.001), but not to the systolic and diastolic blood pressures, and other physical and humoral parameters. CONCLUSIONS: Serum hepatocyte growth factor levels are thought to indicate the presence or development of arteriosclerotic lesions and may be a useful biochemical parameter for estimating the development of systemic arteriosclerosis irrespective of blood pressure levels.