The Role of Glutamate Dehydrogenase Activity in Development of Neurodegenerative Disorders

The specific role of Glutamate dehydrogenase (GLDH) in the brain is not yet clear, but it is an important enzyme in protein degradation as well as a metabolism regulator of glutamate as a neurotransmitter. The enzyme probably provides crucial protection for postsynaptic membranes against the neurotoxic effects of glutamate neurotransmitters. In men, GLDH activity declines almost evenly through the ages;in women, it declines faster in the first five decades. In the years of menopause, GLDH activity declines slower. The diminished GLDH activities in leukocytes and in the brain vary considerably, but they are parallel with the progress of neurodegenerative diseases. The GLDH activity is partly deficient in the brain, particularly in the leukocytes of patients with heterogeneous neurological disorders and degeneration of multiple neuronal systems. We found a statistically significant difference of GLDH activity in the cerebrospinal fluid in patients with neurological diseases and unexpected in patients with degenerative and inflammatory disorders. The decrease in GLDH activity in the cerebrospinal fluid of patients with neurodegenerative disorders may be one of the reasons for the neuro-excito-toxic glutamate effect. Defining the GLDH activity in leukocytes is at the moment the sole experimental method. The second one could be the measurement in cerebrospinal fluid. The results suggest a possibility to regulate glutamate level in human brain through activation of GLDH.

<i>N</i>-Acetylated Gemini Surfactants: Synthesis, Surface-Active Properties, Antifungal Activity, and Ecotoxicity Bioassays

A series of N-acetylated cationic gemini surfactants (3a-e) having dimeric structures derived from tertiary amines were synthesized. Their antifungal potency and surface properties were determined. It also studied the acute toxicity of the molecule with the best performance and the best water solubility (3e) through Chlorella vulgaris and Daphnia magna bioassays. The results were compared to those obtained for a commercially available reference compound 2-(thiocyanomethylthio) benzothiazole (TCMTB). Parameters such as surface tension (&#978CMC), critical micelle concentration (CMC), surface excess concentration (Γ), and area per molecule (A) were determined. The resulting values indicated that the five gemini surfactants are characterized by good surface-active and self-aggregation properties. All surfactants were tested to evaluate their antifungal activity. Six fungal strains were used to conduct the study. The minimum inhibitory concentration (MIC) value was measured by the fungal growth inhibition. The results of the MICs were compared with two commercially available reference compounds (Fluconazole and TCMTB). The least active molecule was 3e, but 3b and 3d were found to be the most potent compounds with a similar activity for all strains. Candida albicans was the most sensitive one. In contrast, Aspergillus niger was resistant. Ecotoxicity of gemini 3e was assessed: the commercial formulation (TCMTB) was between three and four orders of magnitude more toxic than the gemini one for the biological species tested.

Determining the spatial distribution of environmental and socio-economic suitability for human leptospirosis in the face of limited epidemiological data

Background:Leptospirosis is among the leading zoonotic causes of morbidity and mortality worldwide.Knowledge about spatial patterns of diseases and their underlying processes have the potential to guide intervention efforts.However,leptospirosis is often an underreported and misdiagnosed disease and consequently,spatial patterns of the disease remain unclear.In the absence of accurate epidemiological data in the urban agglomeration of Santa Fe,we used a knowledge-based index and cluster analysis to identify spatial patterns of environmental and socioeconomic suitability for the disease and potential underlying processes that shape them.Methods:We geocoded human leptospirosis cases derived from the Argentinian surveillance system during the period 2010 to 2019.Environmental and socioeconomic databases were obtained from satelite images and publicly available platforms on the web.Two sets of human leptospirosis determinants were considered according to the level of their support by the literature and expert knowledge.We used the Zonation algorithm to build a knowledge-based index and a clustering approach to identify distinct potential sets of determinants.Spatial similarity and correlations between index,clusters,and incidence rates were evaluated.Results:We were able to geocode 56.36%of the human leptospirosis cases reported in the national epidemiological database.The knowledge-based index showed the suitability for human leptospirosis in the UA Santa Fe increased from downtown areas of the largest cities towards peri-urban and suburban areas.Cluster analysis revealed downtown areas were characterized by higher levels of socioeconomic conditions.Peri-urban and suburban areas encompassed two clusters which differed in terms of environmental determinants.The highest incidence rates overlapped areas with the highest suitability scores,the strength of association was low though(CSc r=0.21,P<0.001 and ESc r=0.19,P<0.001).Conclusions:We present a method to analyze the environmental and socioeconomic suitability for human leptospirosis based on literature and expert knowledge.The methodology can be thought as an evolutive and perfectible scheme as more studies are performed in the area and novel information regarding determinants of the disease become available.Our approach can be a valuable tool for decision-makers since it can serve as a baseline to plan interventionmeasures.