Axial T2-DRIVE MRI myelography is highly accurate in diagnosing preganglionic traumatic brachial plexus injuries: why pseudomeningoceles should not be used as a primary diagnostic sign.

AIM: To evaluate the accuracy of brachial plexus magnetic resonance imaging (MRI) utilising the three-dimensional (3D)-T2-turbo spin echo (TSE) with 90° flip-back pulse ("DRIVE") myelography in detecting nerve root avulsions in patients with traumatic brachial plexus injuries. MATERIALS AND METHODS: A prospective study of 24 patients planned for brachial plexus reconstructive surgery following trauma from April 2019 to October 2021. Preoperative 1.5 T MRI of the brachial plexus was performed utilising axial T2-DRIVE, looking for signs of avulsions (absent dural rootlets, pauci-rootlet appearance and thickened rootlets; the presence of pseudomeningoceles was noted only as an ancillary sign). Comparison against the reference standard of extra-dural brachial plexus exploration was performed. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated. RESULTS: Eighteen patients had at least one root avulsion at surgery, five showed isolated post-ganglionic injuries, and one had normal brachial plexus exploration. Thirty-nine avulsed roots were found at surgery (out of 108 explored in 24 patients). Preoperative MRI identified the specific avulsed roots accurately in each patient. Two false-positive diagnoses of C5 and C6 avulsions were made in one patient. On MRI, absence of the rootlets was seen in 73.2% (n=30) of avulsions, pauci-rootlet appearance in 24.4% (n=10) and thickening of the rootlets in 2.4% (n=1). Pseudomeningoceles were found only in 68.3% (n=28) of avulsions. The overall sensitivity, specificity, PPV, NPV, and accuracy of MRI were 100%, 97.1%, 95.1%, 100% and 98.1%, respectively. CONCLUSION: 3D-T2-DRIVE is highly accurate in evaluating pre-ganglionic traumatic brachial plexus injuries. Pseudomeningoceles can be considered an ancillary feature of avulsion given the clarity of rootlet visualisation by this sequence.

Recycling of agro-wastes for Ganoderma lucidum mushroom production and Ganoderma post mushroom substrate as soil amendment.

The in vitro growth of Ganoderma mycelia on six agro-wastes namely, broad bean stalks (BBS), cotton stalk (CS), maize straw (MS), rice straw (RS), sugarcane bagasse (SCB) and wheat straw (WS) supplemented with wheat bran (WB) or corn gluten (CG) was evaluated. Among the substrates used, CS appeared best followed by SCB and RS. WB showed best supplementation for mycelial growth. CO2 emission values exhibited accurate measurements to decide the suitability of such agro-waste for growth rather than visual observations. CS+RS+SCB+WB in combination proven its superiority for in vitro growth and active spawn development substrate. In mushroom house, this particular formula proved its superiority and was on par with recommended EG formula; it gave the highest yield (195.16 g Kg-1), biological efficiency (19.52%), protein (16.69%), polysaccharides (3.613%) and minerals (3433 mg/100 g). Spawn running period was the shortest in treatments inoculated with agro-waste-based spawns. With 40% biochar, days required to the complete mycelium colonization and fructification were 10.60 and 23.00, respectively. At 10% biochar, highest yields (238.40 g Kg-1), biological efficiencies (23.84%), protein (19.58%) and minerals (4092 mg/100 g) were obtained. The higher the biochar level, the higher the reduction in emitted CO2, the loss in C and the increase in N of Ganoderma post mushroom substrates (GPMSs). Under greenhouse conditions, almost all the tested GPMSs, at 0.125 or 0.25%, encouraged the reproduction of reniform nematodes and improved plant growth criteria.

Dynamic self-assembly of DNA minor groove-binding ligand DB921 into nanotubes triggered by an alkali halide.

We describe a novel self-assembling supramolecular nanotube system formed by a heterocyclic cationic molecule which was originally designed for its potential as an antiparasitic and DNA sequence recognition agent. Our structural characterisation work indicates that the nanotubes form via a hierarchical assembly mechanism that can be triggered and tuned by well-defined concentrations of simple alkali halide salts in water. The nanotubes assembled in NaCl have inner and outer diameters of ca. 22 nm and 26 nm respectively, with lengths that reach into several microns. Our results suggest the tubes consist of DB921 molecules stacked along the direction of the nanotube long axis. The tubes are stabilised by face-to-face π-π stacking and ionic interactions between the charged amidinium groups of the ligand and the negative halide ions. The assembly process of the nanotubes was followed using small-angle X-ray and neutron scattering, transmission electron microscopy and ultraviolet/visible spectroscopy. Our data demonstrate that assembly occurs through the formation of intermediate ribbon-like structures that in turn form helices that tighten and compact to form the final stable filament. This assembly process was tested using different alkali-metal salts, showing a strong preference for chloride or bromide anions and with little dependency on the type of cation. Our data further demonstrates the existence of a critical anion concentration above which the rate of self-assembly is greatly enhanced.

Phenotypic Screening In Vitro of Novel Aromatic Amidines against Trypanosoma cruzi.

The current treatment of Chagas disease (CD), based on nifurtimox and benznidazole (Bz), is unsatisfactory. In this context, we performed the phenotypic in vitro screening of novel mono- and diamidines and drug interaction assays with selected compounds. Ten novel amidines were tested for their activities against bloodstream trypomastigote (BT) and amastigote forms of Trypanosoma cruzi (Y and Tulahuen strains) and their toxicities for mammalian host cells (L929 cells and cardiac cells). Seven of 10 molecules were more active than Bz against BT, with the most active compound being the diamidine DB2267 (50% effective concentration [EC50] = 0.23 µM; selectivity index = 417), which was 28-fold more active and about 3 times more selective than the standard drug. Five of the six monoamidines were also more active than Bz. The combination of DB2267 and DB2236 in fixed-ratio proportions showed an additive effect (sum of fractional inhibitory concentrations < 4) on BT. Interestingly, when intracellular forms were exposed to DB2267, its activity was dependent on the parasite strain, being effective (EC50 = 0.87 ± 0.05 µM) against a discrete typing unit (DTU) II strain (strain Y) but not against a representative DTU VI strain (strain Tulahuen) even when different vehicles (ß-cyclodextrin and dimethyl sulfoxide) were used. The intrinsic fluorescence of several diamidines allowed their uptake to be studied. Testing of the uptake of DB2236 (inactive) and DB2267 (active) by amastigotes of the Y strain showed that the two compounds were localized intracellularly in different compartments: DB2236 in the cytoplasm and DB2267 in the nucleus. Our present data encourage further studies regarding the activities of amidines and provide information which will help with the identification of novel agents for the treatment of CD.

In vitro investigation of the efficacy of novel diamidines against Trypanosoma cruzi.

Chagas' disease is a neglected tropical disease caused by Trypanosoma cruzi and constitutes a serious public health problem for Latin America. Its unsatisfactory chemotherapy stimulates the search for novel antiparasitic compounds. Amidines and related compounds exhibit well-known activity towards different microbes including T. cruzi. In this vein, our present aim was to evaluate the biological effect of 10 novel structurally related amidines in vitro against bloodstream and intracellular forms of the parasite as well as their potential toxicity on cardiac cell cultures. Our results show that although active against the extracellular forms, with some of them like DB2247 being 6-fold more effective than benznidazole and displaying very low toxicity (>96 µm), none presented superior trypanocidal effect against intracellular forms as compared with the reference drug. These results may be due to differences in susceptibility profiles related to distinct uptake/extrusion mechanisms and cellular targets between bloodstream and amastigote forms. The present study adds to the knowledge base for the future design of novel amidines that may provide promising activity against T. cruzi.

In vitro and in vivo studies of the biological activity of novel arylimidamides against Trypanosoma cruzi.

Fifteen novel arylimidamides (AIAs) (6 bis-amidino and 9 mono-amidino analogues) were assayed against Trypanosoma cruzi in vitro and in vivo. All the bis-AIAs were more effective than the mono-AIAs, and two analogues, DB1967 and DB1989, were further evaluated in vivo. Although both of them reduced parasitemia, protection against mortality was not achieved. Our results show that the number of amidino-terminal units affects the efficacy of arylimidamides against T. cruzi.

The trypanocidal activity of amidine compounds does not correlate with their binding affinity to Trypanosoma cruzi kinetoplast DNA.

Due to limited efficacy and considerable toxicity, the therapy for Chagas' disease is far from being ideal, and thus new compounds are desirable. Diamidines and related compounds such as arylimidamides have promising trypanocidal activity against Trypanosoma cruzi. To better understand the mechanism of action of these heterocyclic cations, we investigated the kinetoplast DNA (kDNA) binding properties and trypanocidal efficacy against T. cruzi of 13 compounds. Four diamidines (DB75, DB569, DB1345, and DB829), eight arylimidamides (DB766, DB749, DB889, DB709, DB613, DB1831, DB1852, and DB2002), and one guanylhydrazone (DB1080) were assayed in thermal denaturation (T(m)) and circular dichroism (CD) studies using whole purified T. cruzi kDNA and a conserved synthetic parasite sequence. The overall CD spectra using the whole kDNA were similar to those found for the conserved sequence and were indicative of minor groove binding. Our findings showed that some of the compounds that exhibited the highest trypanocidal activities (e.g., DB766) caused low or no change in the T(m) measurements. However, while some active compounds, such as DB766, induced profound alterations of kDNA topology, others, like DB1831, although effective, did not result in altered T(m) and CD measurements. Our data suggest that the strong affinity of amidines with kDNA per se is not sufficient to generate and trigger their trypanocidal activity. Cell uptake differences and possibly distinct cellular targets need to be considered in the final evaluation of the mechanisms of action of these compounds.

Is a subset of wrist ganglia the sequela of internal derangements of the wrist joint? MR imaging findings.

PURPOSE: To determine if there is an association between wrist ganglia and internal derangements of the wrist joint by reviewing magnetic resonance (MR) images. MATERIALS AND METHODS: Two observers retrospectively reviewed MR images of the wrist obtained in 625 patients at 1.5 T for the presence of ganglia and associated triangular fibrocartilage complex, scapholunate ligamentous, or lunotriquetral ligamentous tears that were within 3 mm of the ganglion. When available, surgery and/or pathology records were reviewed. RESULTS: There were 122 ganglia and 37 internal derangements. Of the 22 ulnar-sided ganglia, 10 (45%) demonstrated associated triangular fibrocartilage complex tears. Of the 97 radial-sided ganglia, 27 (28%) demonstrated ligamentous tears related to the site of the ganglion. The radial-sided tears involved the radial aspect of the triangular fibrocartilage complex in 12 ganglia; the scapholunate ligament, in isolation, in eight ganglia; and both the triangular fibrocartilage complex and the scapholunate ligament in six ganglia. Only one of the ganglia demonstrated an associated lunotriquetral ligamentous tear. Surgical findings confirmed the ligamentous tears in 25 patients. CONCLUSION: Wrist ganglia are associated, not infrequently, with internal derangements of the wrist.

Production of pro-inflammatory cytokines (GM-CSF, IL-8 and IL-6) by monocytes from fasciolosis patients.

The production of pro-inflammatory cytokines by monocytes in vitro has been measured in eight patients with acute fasciolosis and 15 patients in the chronic stage of the disease, before and after stimulation by excretory/secretory Fasciola antigen. Results were compared with those of a control group of 12 individuals. The monocytes from patients with acute fasciolosis produced significantly higher levels of GM-CSF, IL-8 and IL-6 as compared to controls. With chronicity, the production of these cytokines was decreased as compared to the acute stage probably due to decreased antigen level in blood. Stimulation of monocytes of healthy control with E/S Fasciola antigen was accompanied with a markedly increased production of pro-inflammatory cytokines, while monocytes from patients with acute or chronic fasciolosis revealed minimal increase in production. This denoted the importance of E/S Fasciola antigen as an activator of monocytes. A second exposure to the same antigen was accompanied with a limited response.

Interactions between exogenous luteinizing hormone (hCG), prolactin and prostaglandin F2 alpha on serum enzymes in the rat.

The effect of exogenous luteinizing hormone (hCG), prolactin and prostaglandin F2 alpha, separately or in combination, on the activities of alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase in rat serum was studied. The changes of enzyme activities varied with the different hormones. Luteinizing hormone hCG and prolactin acted synergistically or antagonistically, depending on the enzyme response. Prostaglandin F2 alpha did not seem to modulate the effect of luteinizing hormone (hCG).

Further studies on prostaglandins. III. Effect of prostaglandins on thyroid activity as assessed by 125I.

The effect of crude prostaglandins extraced from prostate glands of camels as well as that PGE1, on the thyroid activity of male immature Boskat rabbits, was investigated. The iodinated amino acid fractions (T1, T2, T3 and T4) in the serum of the injected groups were determined in control and treated animals. Cytological work on sections of the thyroid glands of the treated and control rabbits were performed to study the effect on subcellular level. The results indicate that both crude and pure prostaglandins have a stimulating effect on thyroid activity. This was indicated by the increased 125I uptake of the thyroids of rabbits and evidenced histologically. PGE1, was found to be more effective as compared with the crude prostaglandins. The indinated amino acid and hormone fractions in the serum of the treated groups showed that T2 was increased as a result of injection of the crude prostaglandins, and T4 was increased after PGE1 injection. Tables and figures explained diversed effect.