Revisiting aminocoumarins for the treatment of melioidosis.

Burkholderia pseudomallei causes melioidosis, a potentially lethal disease that can establish both chronic and acute infections in humans. It is inherently recalcitrant to many antibiotics, there is a paucity of effective treatment options and there is no vaccine. In the present study, the efficacies of selected aminocoumarin compounds, DNA gyrase inhibitors that were discovered in the 1950s but are not in clinical use for the treatment of melioidosis were investigated. Clorobiocin and coumermycin were shown to be particularly effective in treating B. pseudomallei infection in vivo. A novel formulation with dl-tryptophan or l-tyrosine was shown to further enhance aminocoumarin potency in vivo. It was demonstrated that coumermycin has superior pharmacokinetic properties compared with novobiocin, and the coumermycin in l-tyrosine formulation can be used as an effective treatment for acute respiratory melioidosis in a murine model. Repurposing of existing approved antibiotics offers new resources in a challenging era of drug development and antimicrobial resistance.

Influenza outbreaks in nursing homes with high vaccination coverage in Navarre, Spain, 2011/12.

In the 2011/12 season, three influenza outbreaks were studied in nursing homes with high vaccination coverage in Navarre, Spain. Attack rates ranged from 2.9% to 67%. Influenza A/Stockholm/18/2011(H3N2) virus strain was isolated from the three outbreaks. Vaccination should be complemented with other hygiene measures in nursing homes. Early detection of influenza outbreaks in nursing homes can aid in their control.

Minimizing creatine kinase variability in rats for neuromuscular research purposes.

Rat serum or plasma creatine kinase (CK) activity is widely used to evaluate myopathic processes, to test the myotoxicity of different drugs, or to analyse the benefits of emerging gene therapies in some neuromuscular disorders. However, great variability is found in this determination. The aim of this study has been to control some factors of variation in order to reduce variability and increase the reproducibility of analytical data. 8-10-week-old Wistar-Han rats were used. The study consisted of four sequential phases. Phase I aimed to analyse the effect of ether and isoflurane as anaesthetic drugs. The objective of Phase II was to evaluate bleeding rats via retro-orbital sinus vs. tail vein. Phases III and IV were designed as two separate, repeated measure experiments on two factors: habituation to laboratory handling procedures in Phase III and gender in Phase IV. The repeated factor was the storage temperature of blood sample prior to centrifugation. Ether did not significantly increased the CK value. Using isoflurane, getting rats accustomed to laboratory handling procedures and whole blood refrigeration prior to centrifugation and serum separation resulted in statistically significant reduction in CK value and variability. Male rats showed significantly higher values than female rats. In the light of our findings, CK value and variability in rats may be minimized by choosing tail vein as site of bleeding, getting rats accustomed to laboratory handling procedures and maintaining whole blood refrigerated until centrifugation and serum separation.

[Correlation between clinical and laboratory data in depression. Therapeutic orientation by means of vitamins and amino acids]. / La correlación entre la clínica y los datos de laboratorio en las depresiones. Orientación terapéutica mediante vitaminas y aminoácidos.

This work is based upon the study of 472 cases from author's private practice. We considered the three following starting points: a) Catecholaminic hypothesis of depressive disorders such as formulated by late Prof. E. Fischer. b) Biochemical analysis of neuro transmitters according to H. Spatz and Mattock to study clinical and laboratory correlation and guide therapy. c) Biological psychiatry's practice and experience in our empirical definition of a final metabolic response to the patients situation. We would like to stress the following conclusions resulting from this investigation: first, the efficacy without unwanted side effects of the formula described as treatment B in the special paragraph; second, a stronger response to tricyclics or Maois when the formula is also administered; third, the confirmation of previous reports pointing out low PEA urinary elimination in those patients with clinical diagnoses different from endogenous depression.

La correlación entre la clínica y los datos de laboratorio en las depresiones. Orientación terapéutica mediante vitaminas y aminoácidos. / [Correlation between clinical and laboratory data in depression. Therapeutic orientation by means of vitamins and amino acids]

This work is based upon the study of 472 cases from authors private practice. We considered the three following starting points: a) Catecholaminic hypothesis of depressive disorders such as formulated by late Prof. E. Fischer. b) Biochemical analysis of neuro transmitters according to H. Spatz and Mattock to study clinical and laboratory correlation and guide therapy. c) Biological psychiatrys practice and experience in our empirical definition of a final metabolic response to the patients situation. We would like to stress the following conclusions resulting from this investigation: first, the efficacy without unwanted side effects of the formula described as treatment B in the special paragraph; second, a stronger response to tricyclics or Maois when the formula is also administered; third, the confirmation of previous reports pointing out low PEA urinary elimination in those patients with clinical diagnoses different from endogenous depression.