Beta-blockade antagonism of tyramine-induced rise in blood pressure

Summary The effect -adrenoceptor blockade on the pressor response to tyramine has been investigated in 6 healthy volunteers, each submitted to an i.v. tyramine pressor test before and after 7 days of propranolol 40 mg b.d. or indenolol 60 mg o.d. Tyramine was given as i.v. boluses of 1–6 mg, alternating with saline, in a randomized, single blind fashion.Prior to treatment tyramine caused a temporary, dose-dependent increase in systolic and diastolic blood pressure, whilst the heart rate remained unaffected. Both propranolol and indenolol reduced the pressor response to tyramine, as shown by a significant increase in ED₁₅, i.e. the dose of tyramine required to increase systolic blood pressure by 15%.     

Factors That Predict 1-Year Incident Hip and Non-Hip Fractures for Home Care Recipients: A Linked-Data Retrospective Cohort Study

ObjectivesThe purpose of our study was to identify factors that predict 1-year incident hip and major osteoporotic non-hip fractures (ie, wrist, spine, pelvis, humerus) for home care recipients while accounting for the competing risk of death.DesignWe conducted a retrospective cohort study with linked population data.Setting and ParticipantsAll home care recipients in Ontario, Canada, receiving services for more than 6 months with an admission assessment between April 1, 2011, and March 31, 2015, were included.MethodsClinical data from the Resident Assessment Instrument Home Care were linked to fracture data from the Discharge Abstract Database and the National Acute Care Reporting System. Competing risk proportional hazard regressions using the Fine and Grey method were performed to model the association between potential risk factors and fracture.ResultsPrevious fall, previous fracture, cognitive impairment, unsteady gait, alcohol use, tobacco use, and Parkinson disease were consistently associated with all fracture types. Cognitive impairment (hazard ratio 2.09; 95% confidence interval 1.86–2.36) and wandering [1.66 (1.06–1.27)] were most predictive of hip fractures and being female [1.86 (1.76–1.98)] and experiencing a previous fracture [1.86 (1.76–1.98)] were most predictive of non-hip fractures. Risk factors unique to non-hip fractures as compared with hip fractures were locomotion ability outdoors and psychotropic medication use.Conclusions and ImplicationsOur results indicate that, in addition to typical fracture risk factors, home care recipients have unique characteristics that increase their risk. Fracture risk assessment tools and subsequent prevention strategies should be modified to accurately identify home care recipients at risk for imminent 1-year fracture.     

Prognostic factors correlated with survival in AIDS patients

The authors present the AIDS cases (CDC '93) observed in Brescia from 1983 to 1994. They observed 1189 subjects (M 84%, F 16%) with a mean age of 32.7 years (intra-venous drug users 75.1%, heterosexuals 14%, homosexuals 9.6%). The mean survival observed was 56.7 weeks from the diagnosis of AIDS (mortality per year 78%). The most frequent AIDS-defining events were Visceral Candidiasis, P.carinii Pneumonia (PCP) and Neurotoxoplasmosis, while the longest and shortest mean survival was for Kaposi's Sarcoma (89 weeks) and Wasting Syndrome (8.4). The mean value of CD4+ lymphocyte counts on AIDS diagnosis was 72.6/l (1166 cases) and the highest and lowest were in non-Hodgkin's Lymphoma (NHL; 147.6/l) and Cryptosporidiosis (18.8/l). Antiretroviral therapy had been given for at least a month in 41.4% subjects (mean treatment duration of 74.8 weeks). The Cox model has demonstrated the favourable effect on survival of high CD4+ lymphocyte counts on diagnosis, antiretroviral therapy, the diagnosis of Tuberculosis (TBC) and PCP as initial markers and the diagnosis of TBC, PCP or Cytomegalovirus infection (CMV) during the entire clinical evolution. Moreover, the unfavourable effect of high age, diagnosis of Progressive Multifocal Leucoencephalopathy (PML), Wasting Syndrome and NHL as initial markers and diagnosis of PML or NHL in any moment of the disease has been demonstrated.     

Prenatal effects of natural calcium supplement on Wistar rats during organogenesis period of pregnancy

The potential of oral exposure to calcium and magnesium citrate, a natural product obtained from dolomite, to initiate teratogenesis was analyzed in Wistar rats. Animals received calcium and magnesium citrate oral doses of 250, 500 and 1000 mg/kg during the period of gestation from day 6 to 17 post conception. Maternal, embryo and fetal toxicity was evaluated. Calcium and magnesium citrate exposure did not produce maternal toxicity assessed by clinical observations, body weight gain, food intake, hematology, biochemical parameters and necropsy finding. Signs of embryo–fetal toxicity were not observed. Skeletal and visceral malformations were seen occasionally in all drug-treated and control groups. Skeletal and visceral variations were similar in control and drug-treated groups except for incomplete ossification rib. These finding was spontaneous and unrelated to the drug. In conclusion, in this study we found that the oral exposure to rats of up to 1000 mg/kg of calcium and magnesium citrate during organogenesis did not induce significant maternal and embryo–fetal toxicity. The experimentally derived NOAEL for developmental toxicity was 1000 mg/kg.     

Metformin Prevented Dopaminergic Neurotoxicity Induced by 3,4-Methylenedioxymethamphetamine Administration

Metformin, a well-known antidiabetic drug, has recently been proposed to promote neurogenesis and to have a neuroprotective effect on the neurodegenerative processes induced by the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in models of Parkinson’s disease. Interestingly, metformin has antioxidant properties and is involved in regulating the production of cytokines released during the neuroinflammatory process. Several studies have reported that 3,4-methylenedioxymethamphetamine (MDMA), a recreational drug mostly consumed by young adults, produces a persistent loss of dopaminergic neurons in the substantia nigra pars compacta (SNc) and caudate putamen (CPu) of mice. The aim of this study was to investigate the potential neuroprotective effect of metformin against short- and long-term neurotoxicity induced by MDMA and its role on MDMA-induced hyperthermia. Adult mice received metformin (2 × 200 mg/kg, 11-h intervals, administered orally), MDMA (4 × 20 mg/kg, 2-h interval, administered intraperitoneally), or MDMA plus metformin (2 × 200 mg/kg, 1 h before the first MDMA administration and 4 h after the last). On the second and third day, mice were treated with vehicle or metformin (1 × 200 mg/kg) and sacrificed 48 h and 7 days after the last MDMA administration. The neuroprotective effect of metformin on MDMA-induced dopaminergic damage was evaluated by dopamine transporter (DAT) and tyrosine hydroxylase (TH) immunohistochemistry in SNc and CPu. Metformin prevented the MDMA-induced loss of TH-positive neurons in the SNc and TH- and DAT-positive fibers in CPu, both at 48 h and 7 days after the last MDMA administration. These results show that metformin is neuroprotective against the short- and long-lasting dopaminergic neurodegeneration induced by MDMA.     

Non-life-threatening sepsis: report of two cases

Streptococcus bovis is one of the nonenterococcal species included among the streptococci group D. It is part of the normal bowel flora in humans and animals, but it is also responsible for infectious diseases (10-15% of all cases of bacterial endocarditis). Many cases of bacteremia and metastatic abscesses (spleen, liver, soft tissues, bone, meninges, endocardium) caused by S. bovis were reported as associated with digestive tract diseases, mainly colonic disease, and, in particular colonic neoplasms, or chronic liver diseases. A role in carcinogenesis has been suggested for this microorganism. The authors report two cases of S. bovis sepsis, one associated with colonic neoplasm and the other with liver cirrhosis and gastric carcinoma. Discussion is focused on probable mechanisms that favor gastric colonization and systemic diffusion of S. bovis from the gut in patients with gastrointestinal neoplasms or chronic liver disease and provides clinical recommendations for patients with S. bovis infections.