A PROSPECTIVE STUDY FOR THE EVALUATION OF NERVE CONDUCTION ABNORMALITIES IN NEWLY DIAGNOSED TYPE 2 DIABETIC PATIENTS

Objectives: Peripheral neuropathy is the one of the frequently encountered complication of type 2 diabetes mellitus (T2DM). Although, the prevalence of diabetic peripheral neuropathy is associated with the diabetes duration, in some cases, the state of neuropathy is evident at the time of diagnosis. In this backdrop, the present study was carried out to evaluate the nerve conduction abnormalities in newly diagnosed T2DM. Methods: This was a prospective study carried out on 30 newly diagnosed T2DM within a time range of 1 month. The patient symptoms such as weakness, burning and tingling senzation, hyperesthesia, and foot ulcer and gait abnormalities were recorded. Nerve conduction analysis of upper limb and lower limb of non-dominant hand side was done using neuro pack S1 machine. Results: Thirty newly diagnosed T2DM patients were enrolled in the present study. The mean age of the patients was found to be 58.12±15.28 years. Distal motor latencies were elevated in T2DM patients as compared to the controls (p<0.05). Further, there was significant prolongation of F-wave latencies in the upper and Lower limbs of the patients as compared to the controls (p<0.05). In addition, there was a significant decrease in sensory conduction velocities in T2DM patients as that of the controls (p<0.05). Conclusion: The study concludes that newly diagnosed T2DM is susceptible to DPN with high incidence rates. Hence, it is essential to perform the nerve conduction studies in newly diagnosed T2DM patients for the early detection and better management and also to prevent the complications

Bacterial genotoxins induce T cell senescence

Several types of pathogenic bacteria produce genotoxins that induce DNA damage in host cells. Accumulating evidence suggests that a central function of these genotoxins is to dysregulate the host's immune response, but the underlying mechanisms remain unclear. To address this issue, we investigated the effects of the most widely expressed bacterial genotoxin, the cytolethal distending toxin (CDT), on T cells—the key mediators of adaptive immunity. We show that CDT induces premature senescence in activated CD4 T cells in vitro and provide evidence suggesting that infection with genotoxin-producing bacteria promotes T cell senescence in vivo. Moreover, we demonstrate that genotoxin-induced senescent CD4 T cells assume a senescence-associated secretory phenotype (SASP) which, at least partly, is orchestrated by the ATM-p38 signaling axis. These findings provide insight into the immunomodulatory properties of bacterial genotoxins and uncover a putative link between bacterial infections and T cell senescence

Transport of the Photodynamic Therapy Agent 5-Aminolevulinic Acid by Distinct H ϩ -Coupled Nutrient Carriers Coexpressed in the Small Intestine

ABSTRACT 5-Aminolevulinic acid (ALA) is a prodrug used in photodynamic therapy, fluorescent diagnosis, and fluorescent-guided resection because it leads to accumulation of the photosensitizer protoporphyrin IX (PpIX) in tumor tissues. ALA has good oral bioavailability, but high oral doses are required to obtain selective PpIX accumulation in colonic tumors because accumulation is also observed in normal gut mucosa. Structural similarities between ALA and GABA led us to test the hypothesis that the H ϩ -coupled amino acid transporter PAT1 (SLC36A1) will contribute to luminal ALA uptake. Radiolabel uptake and electrophysiological measurements identified PAT1-mediated H ϩ -coupled ALA symport after heterologous expression in Xenopus oocytes. The selectivity of the nontransported inhibitors 5-hydroxytryptophan and 4-aminomethylbenzoic acid for, respectively, PAT1 and the H ϩ -coupled di/tripeptide transporter PepT1 (SLC15A1) were examined. 5-Hydroxytryptophan selectively inhibited PAT1-mediated amino acid uptake across the brush-border membrane of the human intestinal (Caco-2) epithelium whereas 4-aminomethylbenzoic acid selectively inhibited PepT1-mediated dipeptide uptake. The inhibitory effects of 5-hydroxytryptophan and 4-aminomethylbenzoic acid were additive, demonstrating that both PAT1 and PepT1 contribute to intestinal transport of ALA. This is the first demonstration of overlap in substrate specificity between these distinct transporters for amino acids and dipeptides. PAT1 and PepT1 expression was monitored by reverse transcriptase-polymerase chain reaction using paired samples of normal and cancer tissue from human colon. mRNA for both transporters was detected. PepT1 mRNA was increased 2.3-fold in cancer tissues. Thus, increased PepT1 expression in colonic cancer could contribute to the increased PpIX accumulation observed. Selective inhibition of PAT1 could enhance PpIX loading in tumor tissue relative to that in normal tissue

An Estimate of the Numbers and Density of Low-Energy Structures (or Decoys) in the Conformational Landscape of Proteins

The conformational energy landscape of a protein, as calculated by known potential energy functions, has several minima, and one of these corresponds to its native structure. It is however difficult to comprehensively estimate the actual numbers of low energy structures (or decoys), the relationships between them, and how the numbers scale with the size of the protein.We have developed an algorithm to rapidly and efficiently identify the low energy conformers of oligo peptides by using mutually orthogonal Latin squares to sample the potential energy hyper surface. Using this algorithm, and the ECEPP/3 potential function, we have made an exhaustive enumeration of the low-energy structures of peptides of different lengths, and have extrapolated these results to larger polypeptides.We show that the number of native-like structures for a polypeptide is, in general, an exponential function of its sequence length. The density of these structures in conformational space remains more or less constant and all the increase appears to come from an expansion in the volume of the space. These results are consistent with earlier reports that were based on other models and techniques

Sodium-coupled Monocarboxylate Transporters in Normal Tissues and in Cancer

SLC5A8 and SLC5A12 are sodium-coupled monocarboxylate transporters (SMCTs), the former being a high-affinity type and the latter a low-affinity type. Both transport a variety of monocarboxylates in a Na+-coupled manner. They are expressed in the gastrointestinal tract, kidney, thyroid, brain, and retina. SLC5A8 is localized to the apical membrane of epithelial cells lining the intestinal tract and proximal tubule. In the brain and retina, its expression is restricted to neurons and the retinal pigment epithelium. The physiologic functions of SLC5A8 include absorption of short-chain fatty acids in the colon and small intestine, reabsorption of lactate and pyruvate in the kidney, and cellular uptake of lactate and ketone bodies in neurons. It also transports the B-complex vitamin nicotinate. SLC5A12 is also localized to the apical membrane of epithelial cells lining the intestinal tract and proximal tubule. In the brain and retina, its expression is restricted to astrocytes and Müller cells. SLC5A8 also functions as a tumor suppressor; its expression is silenced in tumors of colon, thyroid, stomach, kidney, and brain. The tumor-suppressive function is related to its ability to mediate concentrative uptake of butyrate, propionate, and pyruvate, all of which are inhibitors of histone deacetylases. SLC5A8 can also transport a variety of pharmacologically relevant monocarboxylates, including salicylates, benzoate, and γ-hydroxybutyrate. Non-steroidal anti-inflammatory drugs such as ibuprofen, ketoprofen, and fenoprofen, also interact with SLC5A8. These drugs are not transportable substrates for SLC5A8, but instead function as blockers of the transporter. Relatively less is known on the role of SLC5A12 in drug transport

In vitro evaluation of Mucuna pruriens (L.) DC. antioxidant activity

Mucuna pruriens (L). Dc is a plant of the Fabaceae family, commonly known as velvet bean, itchy bean, chiporro bean, mucuna, among others. This plant has several medicinal properties, including its potential to treat Parkinson's disease (PD). International studies have shown that this plant surpasses the benefits of the substance levodopa in the treatment of PD. Taking into account that nerve cells are highly sensitive to oxidative substances, this study evaluated the antioxidant activity of mucuna and compared it to that of levodopa. The plant seeds' phenolic concentration was quantified by using the Folin-Denis reagent and the antioxidant activity assays were performed by using three different methods: the reduction of the phosphomolybdenium complex, the reduction of radical 1,1-diphenyl-2-picrylhydrazyl (DPPH•) and the formation of radical monocation ABTS•+, from the acid [2-2'-azinobis (3-ethylbenzothiazoline-6-sulfonate)]. Results showed that M. pruriens presents high antioxidant capacity, although not superior to isolated levodopa antioxidant capacity. Therefore, further studies should be performed to elucidate the activity of this plant in humans.A Mucuna pruriens (L). Dc é uma planta da família Fabaceae, conhecida popularmente como feijão-veludo, fava-coceira, feijão chiporro, mucuna, entre outros. Possui diversas propriedades medicinais, entre elas, o tratamento da doença de Parkinson (DP). Estudos internacionais vêm demonstrando que essa planta possui atividade superior à do fármaco levodopa para o tratamento da DP. O presente estudo avaliou a possibilidade da atividade antioxidante dessa planta auxiliar nesses resultados, uma vez que as células nervosas são altamente sensíveis às substâncias oxidativas. Para isto foi quantificada a concentração fenólica da semente da mucuna e os testes empregados para a avaliação da atividade antioxidante foram o teste de redução do complexo fosfomolibdênio, redução do radical 1,1-difenil-2-picril-hidrazil (DPPH•) e a formação do radical monocatiônico ABTS•+, proveniente do ácido [2-2'-azino-bis(3-etil-benzolina-6-sulfonado)]. Essa análise demonstrou que M. pruriens possui alta capacidade antioxidante, no entanto, não superior à levodopa isolada e, portanto, novos estudos devem ser realizados para a elucidação da atividade dessa planta em seres humanos

Chitosan Schiff base Ruthenium(III) complexes

Chitosan can be modified chemically by condensation reaction of deacetylated chitosan with aldehydein homogeneous phase. This condensation is carried by primary amine ( NH2) with aldehyde ( CHO)to form corresponding schiff base. The chitosan biopolymer schiff base derivatives are synthesized withsubstituted aldehydes namely 4-hydroxy-3-methoxy benzaldehyde, 2-hydroxy benzaldehyde, and 2-hydroxy-3-methoxy benzaldehyde, becomes a complexing agent or ligand. The Ruthenium(III) complexeswere obtained by complexation of Ruthenium with schiff base ligands and this product exhibits as anexcellent solubility and more biocompatibility. The novel series of schiff base Ruthenium(III) complexesare characterized by Elemental analysis, FT-IR spectroscopy, and Thermo-gravimetric analysis (TGA). Thesynthesized complexes have been subjected to antibacterial study. The antibacterial results indicated thatthe antibacterial activity of the complexes were more effective against Gram positive and Gram negativepathogenic bacteria. These findings are giving suitable support for developing new antibacterial agentand expand our scope for applications