Anaplasma phagocytophila and protozoans of Babesia genus in dogs from endemic areas of Lyme disease in north-western Poland

Infections caused by the spirochete Borrelia burgdorferi sensu lato may be accompanied by other microorganisms, such as Anaplasma, Ehrlichia and Babesia. These pathogens are transmitted by the ticks and are a risk to humans and animals. Ixodes ricinus ticks collected from recreational areas of Szczecin and northwestern Poland contained DNA of the pathogens mentioned above and cases of double and triple coinfection have been documented. The aim of this paper was to determine if dogs suspect to tick infestation in the area of study are a reservoir for these pathogens and to examine the possibility of coinfection. Canine blood was sampled, part of the material originated from dogs exhibiting symptoms of borreliosis. In an earlier study, the samples were screened for DNA from B. burgdorferi sensu lato. In order to screen for A. phagocytophila and Babesia sp. DNA, a PCR-based method was used with the following primers: EHR521/EHR747 for Anaplasma and FOR1/REV1 for Babesia. In 192 samples only two contained A. phagocytophila DNA. One of these samples originated from a healthy canine, the other from an individual with symptoms of borreliosis. The examined samples were not positive for Babesia sp. DNA. Coinfection was not discovered. The low level of A. phagocytophila infection may indicate that the domestic dog is not a reservoir for Anaplasma and Babesia in Szczecin and northwestern Poland. Moreover, this area does not have populations of the brown dog tick (Rhipicephalus sanguineus) or Dermacentor reticulates--both of which are vectors of E. canis and B. canis and commonly induce ehrlichiosis and babesiosis in canines.     

Dermatosis bullosa in patient with chronic renal failure under hemodialysis treatment--case report

A case of 45-year-old patient with chronic renal failure treated by hemodialysis associated with skin changes typical for porphyria cutanea tarda is reported. The diagnosis was based on clinical manifestations and on histopathologic examination of the skin segment. The skin was low sensitive for UVA rays, serum levels of aluminium and lead were significantly elevated. We did not find porphyrins in the urine (24-hour collection 100 ml) as well as in the dialysis fluid.     

Thiazolidinediones under preclinical and early clinical development for the treatment of Parkinson’s disease

Introduction: Current treatment of Parkinson’s disease (PD) is limited to symptomatic dopaminergic therapy, while no interventions have been shown to slow down disease progression.

Areas covered: The following article highlights a group of PPAR-γ agonists called thiazolidinediones (TZDs), which are currently being tested for a putative disease-modifying benefit in PD, using pioglitazone as a prototypic compound. PPAR-γ is highly expressed in neurons of the substantia nigra and CNS immune cells. Preclinical data in rodent and primate support an effect of TZDs in preventing and/or arresting neurodegeneration and development of motor symptoms. Although no data on the neuroprotective effect of TZDs is currently available, a clinical trial is ongoing where the primary objective is to assess pioglitazone’s impact on the progression of PD. The trial is also evaluating the drug’s safety concerns.

Expert opinion: The efficacy data from clinical trials must be carefully weighed against the safety concerns. However, given the solid preclinical data, and since the safety data are not yet fully conclusive and limited to the diabetic population, PPAR-γ research in PD can continue with caution. Ideally, drug discovery and development efforts will lead to the identification of new compounds with reduced risk of peripheral side effects.     

Ixazomib for the treatment of multiple myeloma

Introduction: Proteasome inhibition is a mainstay in the treatment of multiple myeloma (MM). Bortezomib, the first proteasome inhibitor (PI) approved for MM therapy, has shown efficacy in relapsed/refractory patients and in the front-line setting. Among second-generation PIs, MLN9708 (ixazomib) is the first oral compound to be evaluated in MM treatment and has shown improvement in pharmacokinetic and pharmacodynamic parameters compared with bortezomib with a similar efficacy in the control of myeloma growth and in the prevention of bone loss.

Areas covered: In this review, the authors discuss the rationale for use of PIs. They then summarize the clinical development of ixazomib in MM, from initial Phase I to Phase II studies as a monotherapy and in combination with other chemotherapeutics.

Expert opinion: Preliminary data of Phase I/II trials showed that ixazomib had a good safety profile and exerted anti-myeloma activity as a single agent in relapsed/refractory patients. Furthermore, ixazomib also had efficacy in patients who were refractory to bortezomib. Its use in combination with lenalidomide and dexamethasone was shown to be an effective and well-tolerated regimen in up-front treatment leading to minimal residual disease negativity in a significant number of patients. Results of Phase III trials, evaluating ixazomib in induction or maintenance therapy, are awaited.