Iron as the concert master in the pathogenic orchestra playing in sporadic Parkinson's disease.

About 60 years ago, the discovery of a deficiency of dopamine in the nigro-striatal system led to a variety of symptomatic therapeutic strategies to supplement dopamine and to substantially improve the quality of life of patients with Parkinson's disease (PD). Since these seminal developments, neuropathological, neurochemical, molecular biological and genetic discoveries contributed to elucidate the pathology of PD. Oxidative stress, the consequences of reactive oxidative species, reduced antioxidative capacity including loss of glutathione, excitotoxicity, mitochondrial dysfunction, proteasomal dysfunction, apoptosis, lysosomal dysfunction, autophagy, suggested to be causal for ɑ-synuclein fibril formation and aggregation and contributing to neuroinflammation and neural cell death underlying this devastating disorder. However, there are no final conclusions about the triggered pathological mechanism(s) and the follow-up of pathological dysfunctions. Nevertheless, it is a fact, that iron, a major component of oxidative reactions, as well as neuromelanin, the major intraneuronal chelator of iron, undergo an age-dependent increase. And ageing is a major risk factor for PD. Iron is significantly increased in the substantia nigra pars compacta (SNpc) of PD. Reasons for this finding include disturbances in iron-related import and export mechanisms across the blood-brain barrier (BBB), localized opening of the BBB at the nigro-striatal tract including brain vessel pathology. Whether this pathology is of primary or secondary importance is not known. We assume that there is a better fit to the top-down hypotheses and pathogens entering the brain via the olfactory system, then to the bottom-up (gut-brain) hypothesis of PD pathology. Triggers for the bottom-up, the dual-hit and the top-down pathologies include chemicals, viruses and bacteria. If so, hepcidin, a regulator of iron absorption and its distribution into tissues, is suggested to play a major role in the pathogenesis of iron dyshomeostasis and risk for initiating and progressing ɑ-synuclein pathology. The role of glial components to the pathology of PD is still unknown. However, the dramatic loss of glutathione (GSH), which is mainly synthesized in glia, suggests dysfunction of this process, or GSH uptake into neurons. Loss of GSH and increase in SNpc iron concentration have been suggested to be early, may be even pre-symptomatic processes in the pathology of PD, despite the fact that they are progression factors. The role of glial ferritin isoforms has not been studied so far in detail in human post-mortem brain tissue and a close insight into their role in PD is called upon. In conclusion, "iron" is a major player in the pathology of PD. Selective chelation of excess iron at the site of the substantia nigra, where a dysfunction of the BBB is suggested, with peripherally acting iron chelators is suggested to contribute to the portfolio and therapeutic armamentarium of anti-Parkinson medications.

New organophilic kaolin clays based on single-point grafted 3-aminopropyl dimethylethoxysilane.

In this study, the organophilization procedure of kaolin rocks with a monofunctional ethoxysilane- 3 aminopropyl dimethyl ethoxysilane (APMS) is depicted for the first time. The two-step organophilization procedure, including dimethyl sulfoxide intercalation and APMS grafting onto the inner hydroxyl surface of kaolinite (the mineral) layers was tested for three sources of kaolin rocks (KR, KC and KD) with various morphologies and kaolinite compositions. The load of APMS in the kaolinite interlayer space was higher than that of 3-aminopropyl triethoxysilane (APTS) due to the single-point grafting nature of the organophilization reaction. A higher long-distance order of kaolinite layers with low staking was obtained for the APMS, due to a more controllable organiphilization reaction. Last but not least, the solid state (29)Si-NMR tests confirmed the single-point grafting mechanism of APMS, corroborating monodentate fixation on the kaolinite hydroxyl facets, with no contribution to the bidentate or tridentate fixation as observed for APTS.

Small intestinal bacterial overgrowth is associated to symptoms in irritable bowel syndrome. Evidence from a multicentre study in Romania.

BACKGROUND AND AIMS: Small intestinal bacterial overgrowth (SIBO) is involved in the pathogenesis of irritable bowel syndrome (IBS). It has been suggested that by treating SIBO in IBS, symptoms may be improved. The aim of this study was to evaluate the prevalence of SIBO in patients with IBS compared with healthy volunteers (HV), to assess the effect of an intestinal antibiotic in eradicating SIBO and on the symptoms, in patients with IBS. METHODS: Design: a cross-sectional multicentre study with cohort comparison performed in 6 medical centers from Romania. 331 consecutive patients diagnosed with IBS according to Rome III criteria and 105 HV were screened for SIBO using glucose hydrogen breath test (GHBT). Positive patients received 7 days therapy with the antibiotic rifaximin 1200 mg/day and were retested 1 week after completing the treatment. The IBS symptoms were assessed before and after treatment. The group was controlled with 20 age and sex matched IBS patients who did not receive any antibiotic therapy for their condition (control patients). RESULTS: SIBO was found in 105 patients with IBS (31.7%) and in 7 HV (6.6%) (OR= 6.5, p < 0.0001). Patients with IBS have been classified according to Rome III criteria into 4 groups: IBS-constipation, IBS-diarrhea, IBS-mixed (alternation of constipation/and diarrhea) and IBS-unclassified. Diarrhea and mixed symptoms were found to be predictive for SIBO (OR= 2.5 for IBS-diarrhea and OR = 2.23 for mixed). Among patients with SIBO, 85.5% were found negative after treatment (p = 0.0026). SIBO patients showed an important relief of their symptoms, with complete improvement in 46.6% and partial in 31.4%. CONCLUSIONS: This study is the first to estimate the prevalence of SIBO in ibs patients from Romania (31.7%). SIBO was present in nearly half of the IBS-D patients (45.7%). Rifaximin is effective in treating SIBO in IBS patients and controlled trials are warranted.