Lithium and strontium accumulation in native and invasive plants of the Sava River: Implications for bioindication and phytoremediation.

The objective of this study was to investigate the potential of native and invasive plant species for the uptake and accumulation of lithium (Li) and strontium (Sr) along the Sava River, focusing on their bioindication and phytoremediation capabilities. Sampling was carried out in riparian zones exposed to different pollution sources in Slovenia, Croatia, and Serbia. Plant samples of native (Salix alba, Populus alba, Populus nigra, Ulmus glabra, Juglans regia) and invasive (Amorpha fruticosa, Reynoutria japonica, Solidago canadensis, Impatiens glandulifera) species were collected. The content of Li and Sr was analyzed in the soils, roots, and leaves of the selected plants, as well as physical and chemical soil properties. Both Li and Sr content in the soils increased from the source to the mouth of the Sava River. The native species showed significant potential for Li and Sr accumulation based on the metal accumulation index. The highest Sr accumulation was measured in the leaves of Salix alba and the roots of Juglans regia, while the highest Li accumulation was measured in Ulmus glabra. Native species, especially Salix alba, proved to be better bioindicators of Li and Sr. Invasive species, especially Amorpha fruticosa and Impatiens glandulifera, showed a remarkable ability to translocate Sr and Li, respectively, to leaves. These results provide valuable insight into the suitability of plants for biomonitoring soil contamination and potential applications in phytoremediation strategies. In summary, the study shows the importance of native species in the context of the accumulation and bioindication of soil pollution.

Analysis of PMP22 duplication and deletion using a panel of six dinucleotide tandem repeats.

BACKGROUND: Charcot-Marie-Tooth type 1A (CMT1A) is the most common type of hereditary motor and sensory neuropathies (HMSN), caused by the duplication of the 17p11.2 region that includes the PMP22 gene. Reciprocal deletion of the same region is the main cause of hereditary neuropathy with liability to pressure palsies (HNPP). CMT1A accounts for approximately 50% of HMSN patients. Diagnostics of CMT1A and HNPP are based on quantitative analysis of the affected region or RFLP detection of breakage points. The aim of this study was to improve the sensitivity and efficiency of CMT1A and HNPP genetic diagnostics by introducing analysis of six STR markers (D17S261-D17S122-D17S839-D17S1358-D17S955-D17S921) spanning the duplicated region. METHODS: Forty-six CMT1A and seven HNPP patients, all genetically diagnosed by RFLP analysis, were tested for duplication or deletion using six STR markers. RESULTS: In all CMT1A and HNPP patients, microsatellite analysis comprising six STR markers confirmed the existence of a duplication or deletion. In 89% (41/46) CMT1A patients the confirmation was based on detecting three alleles on at least one locus. In the remaining 11% (5) CMT1A patients, duplication was also confirmed based on two peaks with clear dosage difference for at least two different markers. All HNPP patients (7/7) displayed only one allele for each analyzed locus. CONCLUSIONS: Microsatellite analysis using six selected STR loci showed a high level of sensitivity and specificity for genetic diagnostics of CMT1A and HNPP. The results here strongly suggest STR marker analysis as a method of choice in PMP22 duplication/deletion testing.

Development of an extended half-life GM-CSF fusion protein for Parkinson's disease.

Transformation of CD4+ T cell effector to regulatory (Teff to Treg) cells have been shown to attenuate disease progression by restoring immunological balance during the onset and progression of neurodegenerative diseases. In our prior studies, we defined a safe and effective pathway to restore this balance by restoring Treg numbers and function through the daily administration of the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF). These studies were conducted as a proof-of-concept testing in Parkinson's disease (PD) preclinical models and early phase I clinical investigations. In both instances, they served to ameliorate disease associated signs and symptoms. However, despite the recorded efficacy, the cytokine's short half-life, low bioavailability, and injection site reactions proved to be limitations for any broader use. To overcome these limitations, mRNA lipid nanoparticles encoding an extended half-life albumin-GM-CSF fusion protein were developed for both mouse (Msa-GM-CSF) and rat (Rsa-GM-CSF). These formulations were tested for immunomodulatory and neuroprotective efficacy using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and human wild-type alpha-synuclein (αSyn) overexpression preclinical models of PD. A single dose of the extended half-life mouse and rat mRNA lipid nanoparticles generated measurable GM-CSF plasma cytokine levels up to four days. Increased Treg frequency and function were associated with a resting microglial phenotype, nigrostriatal neuroprotection, and restoration of brain tissue immune homeostasis. These findings were substantively beyond the recorded efficacy of daily recombinant wild-type GM-CSF with a recorded half-life of six hours. Mechanistic evaluation of neuropathological transcriptional profiles performed in the disease-affected nigral brain region demonstrated an upregulation of neuroprotective CREB and synaptogenesis signaling and neurovascular coupling pathways. These findings highlight the mRNA-encoded albumin GM-CSF fusion protein modification linked to improvements in therapeutic efficacy. The improvements achieved were associated with the medicine's increased bioavailability. Taken together, the data demonstrate that mRNA LNP encoding the extended half-life albumin-GM-CSF fusion protein can serve as a benchmark for PD immune-based therapeutics. This is especially notable for improving adherence of drug regimens in a disease-affected patient population with known tremors and gait abnormalities.

Mutational analysis of GJB1, MPZ, PMP22, EGR2, and LITAF/SIMPLE in Serbian Charcot-Marie-Tooth patients.

We report the results of mutational analysis in the following genes: GJB1, MPZ, PMP22, EGR2, and LITAF/SIMPLE in 57 Charcot-Marie-Tooth (CMT) patients of Serbian origin without the PMP22 duplication. We found 10 different mutations in 14 CMT patients: 6 mutations in GJB1, 3 in MPZ, and 1 in PMP22. Five of six GJB1 mutations are reported for the first time, and the most frequent one appears to be a founder mutation in the Serbian population. No mutations were found in EGR2 or LITAF. Thus, GJB1 mutation analysis should be done in patients without the PMP22 duplication and male-to-male transmission of CMT.

Fixed drug eruption caused by tadalafil--case report.

UNLABELLED: Fixed drug eruptions (FDE) are commonly reported type of mucocutaneous drug eruption. The aim of this paper is to present a patient with multiple mucocutaneous erythema fixum type lesions caused by oral tadalafil use. A short course of topical corticosteroid therapy resulted in complete resolution of all lesions leaving residual hyperpigmentation of the involved skin sites. Mucosal oral lesions were effectively treated with gingival hyaluronic acid 0.2% gel. CONCLUSION: when assessing a patient of any age with drug eruptions, a thorough personal history should be obtained, in particular data on regular or recreational use of phospodiesterase type 5 inhibitors.

An algorithm for genetic testing of Serbian patients with demyelinating Charcot-Marie-Tooth.

Charcot-Marie Tooth (CMT) is a clinically and genetically heterogeneous group of diseases with rough genotype-phenotype correlation, so the final diagnosis requires extensive clinical and electrophysiological examination, family data, and gene mutation analysis. Although there is a common pattern of genetic basis of CMT, there could be some population differences that should be taken into account to facilitate analyses. Here we present the algorithm for genetic testing in Serbian patients with demyelinating CMT, based on their genetic specificities: in cases of no PMP22 duplication, and if -X-linked CMT (CMTX) is not contraindicated by pattern of inheritance (male-to-male transmission), one should test for c.94A>G GJB founder mutation, first. Also, when a patient is of Romani ethnicity, or if there is an autosomal recessive inheritance in a family and unclear ethnicity, c.442C>T mutation in NDRG1 should be tested.

Fixed drug eruption caused by tadalafil - case report / Erupcao fixa por droga provocada por tadalafil - relato de caso

Fixed drug eruptions (FDE) are commonly reported type of mucocutaneous drug eruption. The aim of this paper is to present a patient with multiple mucocutaneous erythema fixum type lesions caused by oral tadalafil use. A short course of topical corticosteroid therapy resulted in complete resolution of all lesions leaving residual hyperpigmentation of the involved skin sites. Mucosal oral lesions were effectively treated with gingival hyaluronic acid 0.2% gel. Conclusion: when assessing a patient of any age with drug eruptions, a thorough personal history should be obtained, in particular data on regular or recreational use of phospodiesterase type 5 inhibitors.

A erupção fixa por droga é um tipo de erupção mucocutânea comumente relatada, provocada pela administração de de drogas. O objetivo deste artigo é apresentar um paciente com múltiplas lesões mucocutâneas do tipo do eritema fixo, causadas pelo uso do tadalafil oral. Um breve período de tratamento com corticosteroides tópicos levou à completa resolução de todas as lesões, deixando hiperpigmentação residual nas áreas cutâneas envolvidas. As lesões da mucosa oral foram tratadas efetivamente com gel de ácido hialurônico gengival a 0,2%. Conclusão: ao avaliar o paciente com erupção fixa por druga, de qualquer idade, deve ser obtido seu histórico pessoal completo, especialmente dados sobre uso regular ou recreativo de inibidores de fosfodiesterase tipo 5.