Berberine Ameliorates Periodontal Bone Loss by Regulating Gut Microbiota.

Postmenopausal osteoporosis (PMO) is a risk factor for periodontitis, and current therapeutics against PMO prevent the aggravated alveolar bone loss of periodontitis in estrogen-deficient women. Gut microbiota is recognized as a promising therapeutic target for PMO. Berberine extracted from Chinese medicinal plants has shown its effectiveness in the treatment of metabolic diseases such as obesity and diabetes via regulating gut microbiota. Here, we hypothesize that berberine ameliorates periodontal bone loss by improving the intestinal barriers by regulating gut microbiota under an estrogen-deficient condition. Experimental periodontitis was established in ovariectomized (OVX) rats, and the OVX-periodontitis rats were treated with berberine for 7 wk before sacrifice for analyses. Micro-computed tomography and histologic analyses showed that berberine treatment significantly reduced alveolar bone loss and improved bone metabolism of OVX-periodontitis rats as compared with the vehicle-treated OVX-periodontitis rats. In parallel, berberine-treated OVX-periodontitis rats harbored a higher abundance of butyrate-producing gut microbiota with elevated butyrate generation, as demonstrated by 16S rRNA sequencing and high-performance liquid chromatography analysis. Berberine-treated OVX-periodontitis rats consistently showed improved intestinal barrier integrity and decreased intestinal paracellular permeability with a lower level of serum endotoxin. In parallel, IL-17A-related immune responses were attenuated in berberine-treated OVX-periodontitis rats with a lower serum level of proinflammatory cytokines and reduced IL-17A+ cells in alveolar bone as compared with vehicle-treated OVX-periodontitis rats. Our data indicate that gut microbiota is a potential target for the treatment of estrogen deficiency-aggravated periodontal bone loss, and berberine represents a promising adjuvant therapeutic by modulating gut microbiota.

Pemetrexed disodium: a novel antifolate clinically active against multiple solid tumors.

Pemetrexed disodium (ALIMTA), "pemetrexed") is a novel, multi-targeted antifolate that has demonstrated promising clinical activity in a wide variety of solid tumors, including non-small cell lung, breast, mesothelioma, colorectal, pancreatic, gastric, bladder, cervix, and head and neck. Pemetrexed inhibits multiple folate-dependent enzymes involved in both purine and pyrimidine synthesis including thymidylate synthase, dihydrofolate reductase, glycinamide ribonucleotide formyltransferase, and aminoimidazole carboxamide ribonucleotide formyltransferase. As a single agent, pemetrexed exhibits a moderate toxicity profile at a dose of 500 mg/m(2) by 10-minute infusion once every 21 days with myelosuppression being the dose-limiting toxicity. Folic acid added to the diet in preclinical studies reduced toxicities while maintaining antitumor activity. Based on this observation and clinical toxicities, folic acid and vitamin B(12) dietary supplementation has been recently introduced into all ongoing trials. Studies combining pemetrexed with other active chemotherapeutic agents demonstrate that these combination therapies may become important treatment regimens in a variety of cancer types. Currently, pemetrexed phase III trials are ongoing in mesothelioma and non-small cell lung cancer with future trials planned to explore this unique multitargeted antifolate.

Incidence of lymphohaematopoietic malignancies in a petrochemical industry cohort: 1983-94 follow up.

OBJECTIVES: In response to a previous finding of increased mortality from lymphohaematopoietic (LH) malignancies, this study examines incidence of LH malignancy in a petrochemical industry cohort. Emphasis is on chronic lymphocytic leukaemia (CLL) and on comparisons by period of first employment. METHOD: The study cohort consists of 8942 employees who were active in the period 1970-92 and alive on 31 December 1982. Record linkage with the Louisiana tumour registry (LTR) provided information on cancer for cases occurring between 1983 and 1994. Standardised incidence ratios (SIR), with the south Louisiana population as a comparison, were computed for all cancers, all LH malignancies and specific LH subtypes. Analyses were conducted for sex and race categories, and by period of first employment, job type, duration of employment, and latency. RESULTS: 672 Cases of cancer were identified, including 59 LH malignancies. Women (n=1169) had an overall cancer SIR below unity and four LH malignancies versus 2.28 expected. Among the 7773 men, those first employed before 1950 had no overall cancer excess, a significant 1.4-fold increase in overall LH malignancies (43 observed versus 30.78 expected), and four CLL cases versus 3.27 expected. Findings for men first employed after 1950 are based on fewer cases, but there was no indication of excesses of overall cancer or LH malignancy. Numbers were too small in the group first employed after 1950 for meaningful analysis of LH malignancy subtypes such as CLL (one case). CONCLUSION: These findings do not suggest a continuing excess of CLL but do suggest a small increase in incidence of overall LH malignancy for workers first employed before 1950. This may reflect associations with earlier workplace conditions, although work related patterns are mixed. Interpretation is limited by the diverse group of diseases within LH malignancies, and the lack of control for non-work factors other than sex, age, race, and period of diagnosis. This study has a major advantage of more complete and reliable cancer ascertainment compared with the mortality investigation, and shows the feasibility and benefits of using cancer registry incidence data in an occupational cohort study.

Moxifloxacin in the therapy of experimental pneumococcal meningitis.

The activity of moxifloxacin (BAY 12-8039) against a Streptococcus pneumoniae type 3 strain (MIC and minimum bactericidal concentration [MBC] of moxifloxacin, 0.06 and 0.25 microgram/ml, respectively; MIC and MBC of ceftriaxone, 0.03 and 0.06 microgram/ml, respectively) was determined in vitro and in a rabbit model of meningitis. Despite comparable bactericidal activity, 10 micrograms of moxifloxacin per ml released lipoteichoic and teichoic acids less rapidly than 10 micrograms of ceftriaxone per ml in vitro. Against experimental meningitis, 10 mg of moxifloxacin per kg of body weight per ml reduced the bacterial titers in cerebrospinal fluid (CSF) almost as rapidly as ceftriaxone did (mean +/- standard deviation, -0.32 +/- 0.14 versus -0.39 +/- 0.11 delta log CFU/ml/h). The activity of moxifloxacin could be described by a sigmoid dose-response curve with a maximum effect of -0.33 delta log CFU/ml/h and with a dosage of 1.4 mg/kg/h producing a half-maximal effect. Maximum tumor necrosis factor activity in CSF was observed later with moxifloxacin than with ceftriaxone (5 versus 2 h after the initiation of treatment). At 10 mg/kg/h, the concentrations of moxifloxacin in CSF were 3.8 +/- 1.2 micrograms/ml. Adjunctive treatment with dexamethasone at 1 mg/kg prior to the initiation of antibiotic treatment only marginally reduced the concentrations of moxifloxacin in CSF (3.3 +/- 0.6 micrograms/ml). In conclusion, moxifloxacin may qualify for use in the treatment of S. pneumoniae meningitis.

Rifabutin for experimental pneumococcal meningitis.

Rifabutin is a lipophilic antibacterial with high in vitro activity against many pathogens involved in bacterial meningitis including pneumococci. Resistance to beta-lactam antibiotics in pneumococci is not associated with a decreased sensitivity to rifabutin (30 strains from Germany with intermediate penicillin resistance; MIC range of penicillin: 0.125-1 mg/l, MIC of rifabutin: < 0.008-0.015 mg/l). Rifabutin at doses of 0.625, 1.25, 2.5, 5 and 10 mg/kg/h i.v. was investigated in a rabbit model of meningitis using a Streptococcus pneumoniae type 3 (MIC/MBC of rifabutin: 0.015/0.06 mg/l). The bacterial density in CSF at the onset of treatment was 7.3 +/- 0.6 log CFU/ml (mean +/- SD). Rifabutin decreased bacterial CSF titers in a dose-dependent manner [delta log CFU/ml/h (slope of the regression line log CFU/ml vs. time) at a dose of 0.625 mg/kg/h: -0.16 +/- 0.06 (n = 3), at 1.25 mg/kg/h: -0.20 +/- 0.12 (n = 4), at 2.5 mg/kg/h: -0.24 +/- 0.04 (n = 4), at 5 mg/kg/h: -0.31 +/- 0.10 (n = 8), and at 10 mg/kg/h: -0.29 +/- 0.10 (n = 5)]. At high doses rifabutin was as active as ceftriaxone at 10 mg/kg/h (delta log CFU/ml/h: -0.29 +/- 0.10, n = 10). Two and 5 h after initiation of therapy, CSF TNF-alpha activities were lower with rifabutin 5 mg/kg/h than with ceftriaxone (medians 2 vs. 141 U/ml, p = 0.005 at 2 h; median 51 vs. 120 U/ml 5 h after initiation of therapy, p = 0.04). This did not result, however, in a decrease of indicators of neuronal damage. In conclusion, intravenous rifabutin was bactericidal in experimental pneumococcal meningitis. Provided that a well-tolerated i.v. formulation will be available it may qualify as a reserve antibiotic for pneumococcal meningitis, in particular when strains with a reduced sensitivity to beta-lactam antibiotics are the causative pathogens.

Black tobacco, maté, and bladder cancer. A case-control study from Uruguay.

A case-control study of bladder cancer involving interviews with 111 incident cases and 222 controls was carried out in Montevideo, Uruguay. The analysis was conducted separately for each sex. Point estimates of relative risk associated with smoking variables, ingestion of infusions of the herb Ilex paraguariensis (maté), and selected dietary items were obtained by stratified and logistic regression analysis. Among men, smokers of black tobacco showed a relative risk (RR) 2.7 higher than blond tobacco smokers and maté exposure showed a significant dose-response, after adjustment for age, residence, social class, hospital, type of tobacco, smoking intensity, smoking duration, and vegetable consumption, with a seven-fold increase in risk for heavy consumers. Joint exposure to type of tobacco and maté consumption showed a multiplicative effect. Women showed a similar increase in risk with maté consumption. The results suggest that the high mortality rates of bladder cancer observed in Uruguay could be explained by the combined effect of black tobacco smoking and maté ingestion.

Red phosphorus as a cause of corneal injury. A case report.

A 15-year-old pupil was injured by an explosive mixture of red phosphorus powder and potassium chlorate causing seeding of multiple foreign bodies upon superficial and deep corneal layers. Unlike the few fulminant cases reported in the English literature our case had a benign course and outcome, without any late complications.

Use of nonblood priming for open-heart surgery in dogs.

Three electrolyte solutions were used as priming perfusates for 1 hour of cardiopulmonary bypass in 9 dogs. Arterial blood pressure was maintained at a satisfactory level during perfusion and returned to the original ranges shortly after bypass. Measurement of various blood constituents indicated that they were constantly maintained in the normal range during the procedure. The PVC decreased sharply until the 3rd postperfusion day, then returned to the base-line values. Similar patterns were obtained for each solution, with no additional infusion being administered after bypass. All dogs recovered without complications and evidence of cerebral abnormalities was not seen. The dogs were euthanatized and necropsied 14 days after surgery and all major organs appeared normal on gross examination.