Recently research shows that horseradish peroxidase, HRP, when combined with other compounds, is highly reactive toward different human tumour cells and that better understanding of catalytic mechanism and inhibition HPR could lead to a new targeted cancer therapy. Thus, the inhibition of HRP activity by dipotassium-trioxohydroxytetrafluorotriborate K2[B3O3F4OH] was investigated for possible explanation of previously observed antitumour activities of this promising drug. HRP activity was studied under steady-state kinetic conditions by a spectrophotometric method. In the absence of the inhibitor values of = 0.47 mM and = 0.34 mM min−1, respectively, were determined. The hydrogen peroxide H2O2 kinetic measurements show a competitive inhibition with the inhibition constant = 2.56 mM. The activation energy values were found to be very similar for both reactions; in the absence of inhibitor activation energy was 17.7 kJ mol−1 and in the presence of inhibitor activation energy was 16.3 kJ mol−1. The values of Arrhenius constants were found to be different; = 4.635 s−1 was measured in the absence of inhibitor while in the presence of inhibitor Arrhenius constant was 1.745 s−1 showing that K2[B3O3F4OH] initiates conformational change in the structure of the HRP and subsequently reduces its activity.

Mitochondria have their own translation machinery that produces key subunits of the OXPHOS complexes. This machinery relies on the coordinated action of nuclear-encoded factors of bacterial origin that are well conserved between humans and yeast. In humans, mutations in these factors can cause diseases; in yeast, mutations abolishing mitochondrial translation destabilize the mitochondrial DNA. We show that when the mitochondrial genome contains no introns, the loss of the yeast factors Mif3 and Rrf1 involved in ribosome recycling neither blocks translation nor destabilizes mitochondrial DNA. Rather, the absence of these factors increases the synthesis of the mitochondrially-encoded subunits Cox1, Cytb and Atp9, while strongly impairing the assembly of OXPHOS complexes IV and V. We further show that in the absence of Rrf1, the COX1 specific translation activator Mss51 accumulates in low molecular weight forms, thought to be the source of the translationally-active form, explaining the increased synthesis of Cox1. We propose that Rrf1 takes part in the coordination between translation and OXPHOS assembly in yeast mitochondria. These interactions between general and specific translation factors might reveal an evolutionary adaptation of the bacterial translation machinery to the set of integral membrane proteins that are translated within mitochondria.

Introduction. Synchronous multicentric cerebral gliomas are uncommon brain tumors, mostly malignant, with unknown pathogenesis, unfavorable prognosis and still controversial management. Preoperative differentiation from other multiple brain pathologies by conventional magnetic resonance imaging (MRI) is often difficult, but supplemental use of advanced magnetic resonance techniques should allow the tumor biology to be predicted, and an appropriate treatment strategy planned. Case report. We report the case of a 59-year-old man with double synchronous multicentric cerebral lesions, which had initial MRI and diffusion-weighted imaging presentation as left parietal metastasis and ipsilateral amygdalo-hippocampal low-grade glioma. However, magnetic resonance spectroscopy (MRS) of both lesions showed different metabolite profiles of malignant glioma. En bloc resection of the easily accessible parietal lesion revealed glioblastoma with methylated O6-methylguanine-DNA methyltransferase (MGMT) gene promoter. Subsequently, the patient was treated with temozolomide (TMZ)-based chemoradiation according to Stupp’s protocol, with continuous standard (5/28) adjuvant TMZ in 12 courses. Despite prolonged stabilization of the disease with good life-quality during treatment, the patient died 19 months after diagnosis. The time to tumor progression estimated by MRI was 17 months. Conclusion. MRS significantly improved the differential diagnostic accuracy of conventional MRI in our patient. In accordance with reviewed literature data, the younger age, good initial performance status and methylated MGMT gene promoter were all favorable predictors of longer survival in the reported case. Resection of at least one easily accessible tumor lesion, followed by TMZ-based chemoradiation, with continuous adjuvant TMZ in more than 6 standard courses, seems currently to be the most beneficial therapeutic option for such cases.

BackgroundPol III-related leukodystrophies, including 4H leukodystrophy, are recently recognized disorders that comprise hypomyelination and various neurologic and non-neurologic clinical manifestations. We report the unique neurologic presentation of the micturition dysfunction in Pol III-related leukodystrophy and describe the novel endocrine abnormalities in this entity.Case presentationA 32-year-old Caucasian female exhibited chronic urinary incontinence that commenced at the age of 7 years and remained the unexplained symptom more than two decades before the onset of progressive neurologic decline. A transient growth failure and absent sexual development with hypoprolactinemia appeared in the meanwhile. Neurologic, endocrine, neuroradiologic, and genetic evaluation performed only in the patient’s thirties, confirmed the diagnosis of 4H leukodystrophy as the only cause of the micturition disturbance.ConclusionThe report shows for the first time that an unexplained chronic bladder dysfunction should be evaluated also as a possible 4H leukodystrophy, thus alerting to the unexpected neurologic and endocrine features in 4H leukodystrophy.