Amino Acid-Based Boron Carriers in Boron Neutron Capture Therapy (BNCT).

Interest in the design of boronated amino acids has emerged, partly due to the utilization of boronophenylalanine (BPA), one of the two agents employed in clinical Boron Neutron Capture Therapy (BNCT). The boronated amino acids synthesized thus far for BNCT investigations can be classified into two categories based on the source of boron: boronic acids or carboranes. Amino acid-based boron carriers, employed in the context of BNCT treatment, demonstrate significant potential in the treatment of challenging tumors, such as those located in the brain. This review aims to shed light on the developmental journey and challenges encountered over the years in the field of amino acid-based boron delivery compound development. The primary focus centers on the utilization of the large amino acid transporter 1 (LAT1) as a target for boron carriers in BNCT. The development of efficient carriers remains a critical objective, addressing challenges related to tumor specificity, effective boron delivery, and rapid clearance from normal tissue and blood. LAT1 presents an intriguing and promising target for boron delivery, given its numerous characteristics that make it well suited for drug delivery into tumor tissues, particularly in the case of brain tumors.

Intrinsically disordered intracellular domains control key features of the mechanically-gated ion channel PIEZO2.

A central question in mechanobiology is how mechanical forces acting in or on cells are transmitted to mechanically-gated PIEZO channels that convert these forces into biochemical signals. Here we examined the role of the intracellular domains of PIEZO2, which account for 25% of the channel, and demonstrate that these domains fine-tune properties such as poking and stretch-sensitivity, velocity coding and single channel conductance. Moreover, we show that the intrinsically disordered linker between the transmembrane helices twelve and thirteen (IDR5) is required for the activation of PIEZO2 by cytoskeleton-transmitted forces. The deletion of IDR5 abolishes PIEZO2-mediated inhibition of neurite outgrowth, while it only partially affected its sensitivity to cell indentation and does not alter its stretch sensitivity. Thus, we propose that PIEZO2 is a polymodal mechanosensor that detects different types of mechanical stimuli via different force transmission pathways, which highlights the importance of utilizing multiple complementary assays when investigating PIEZO function.

(E)-Di-iodination of Alkynes Using Dried Dowex H+/NaI Approach.

We investigated the usefulness of the dried Dowex H+/NaI approach for the selective di-iodination of alkynes. The Dowex H+/NaI approach selectively produces only (E)-di-iodinated products; it is very straightforward and nontoxic. The utilization of 2-propanol as a solvent in the reactions can be considered as a "green" approach and the method maybe extended to radio-iodination. The method allows access to highly important building blocks. An initial example of the di-iodination and esterification in the same one-pot reaction is also presented.

Common Variable Immunodeficiency and Circulating TFH.

CD4+ T follicular helper cells (TFH) were assessed in adult patients with common variable immune deficiency (CVID) classified according to the presence of granulomatous disease (GD), autoimmunity (AI), or both GD and AI (Group I) or the absence of AI and GD (Group II). TFH lymphocytes were characterized by expression of CXCR5 and PD-1. TFH were higher (in both absolute number and percentage) in Group I than in Group II CVID patients and normal controls (N). Within CXCR5+CD4+ T cells, the percentage of PD-1 (+) was higher and that of CCR7 (+) was lower in Group I than in Group II and N. The percentages of Treg and TFH reg were similar in both CVID groups and in N. TFH responded to stimulation increasing the expression of the costimulatory molecules CD40L and ICOS as did N. After submitogenic PHA+IL-2 stimulation, intracellular expression of TFH cytokines (IL-10, IL-21) was higher than N in Group I, and IL-4 was higher than N in Group II. These results suggest that TFH are functional in CVID and highlight the association of increased circulating TFH with AI and GD manifestations.

In vitro aflatoxin B1 binding capacity by two Enterococcus faecium strains isolated from healthy dog faeces.

AIM: This study evaluated the binding capacity of aflatoxin B1 (AFB1 ) by two Enterococcus faecium strains (MF4 and GJ40) isolated from faeces from healthy dogs. MATERIALS AND METHODS: The binding assay was performed using 50 and 100 ppb of AFB1 analysing the effects of the viability, incubation time and pH on AFB1 binding. Binding stability was determined by washing three times the bacteria-AFB1 complexes with phosphate buffer saline. RESULTS: Both GJ40 and MF4 strains have the ability to remove AFB1 from aqueous solution. Viable cells were slightly more effective in AFB1 binding than nonviable ones for both strains. Enterococcus faeciumGJ40 removes 24-27% and 17-24%, and Ent. faeciumMF4 removes 36-42% and 27-32% of AFB1 (50 and 100 ppb, respectively) throughout a 48 h incubation period. In general, the removal of AFB1 was highest at pH 7.00 for both strains. The stability of the bacteria-AFB1 complex formed was found to be high (up to 50% of AFB1 remained bounded in bacterial cell after three washes with phosphate buffered saline). CONCLUSION: The Ent. faecium strains assayed are capable of removing AFB1 under different conditions in vitro. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first AFB1 binding assay performed with Ent. faecium strains isolated from dog faeces, being an interesting strategy for AFB1 decontamination of pet food.

Performance and microbial diversity of palm oil mill effluent microbial fuel cell.

AIM: To evaluate the bioenergy generation and the microbial community structure from palm oil mill effluent using microbial fuel cell. METHODS AND RESULTS: Microbial fuel cells enriched with palm oil mill effluent (POME) were employed to harvest bioenergy from both artificial wastewater containing acetate and complex POME. The microbial fuel cell (MFC) showed maximum power density of 3004 mW m(-2) after continuous feeding with artificial wastewater containing acetate substrate. Subsequent replacement of the acetate substrate with complex substrate of POME recorded maximum power density of 622 mW m(-2). Based on 16S rDNA analyses, relatively higher abundance of Deltaproteobacteria (88.5%) was detected in the MFCs fed with acetate artificial wastewater as compared to POME. Meanwhile, members of Gammaproteobacteria, Epsilonproteobacteria and Betaproteobacteria codominated the microbial consortium of the MFC fed with POME with 21, 20 and 18.5% abundances, respectively. CONCLUSIONS: Enriched electrochemically active bacteria originated from POME demonstrated potential to generate bioenergy from both acetate and complex POME substrates. Further improvements including the development of MFC systems that are able to utilize both fermentative and nonfermentative substrates in POME are needed to maximize the bioenergy generation. SIGNIFICANCE AND IMPACT OF THE STUDY: A better understanding of microbial structure is critical for bioenergy generation from POME using MFC. Data obtained in this study improve our understanding of microbial community structure in conversion of POME to electricity.

Synthesis and anti-inflammatory effects of a series of novel 7-hydroxycoumarin derivatives.

A number of 7-hydroxycoumarins have been synthesised by Pechmann cyclisation using differently substituted resorcinols employing perchloric acid as the condensing agent. All the compounds have been characterised by analytical and spectroscopic methods. The anti-inflammatory properties were tested with LPS-induced inflammation in J774 macrophages. Expression of iNOS and COX-2 was determined by Western blot, NO by nitrite assay and IL-6 by ELISA analyses. Fifteen of the tested 7-hydroxycoumarins also inhibited IL-6 production but none of them had any major inhibitory effect on COX-2 expression.

Population fluctuation of Anopheles (Diptera: Culicidae) in forest and forest edge habitats in Tucumán province, Argentina.

The aim of this work was to study the possible effects of forest and forest edge habitats on the population fluctuation of the Anopheles species in northwestern Argentina, taking into consideration the relationship between this fluctuation and climatic variables. This study is one of the first that involves the Anopheles fauna in the country and its dynamics in two different habitats. Sampling was carried out from October, 2002 to October, 2003, in the forest and on the forest edge. Both habitats were compared for species diversity and abundance, and multiple regression analyses were performed to analyze the effects of environmental variables on the population dynamics. Five hundred and sixteen adult specimens of Anopheles species were collected, the most numerous group being Arribalzaga (52.1%), followed by Anopheles (Nyssorhynchus) strodei (20.5%) and Anopheles (Nyssorhynchus) evansae (6.4%). Mosquito abundance was greatest in the forest, the most productive habitat. Samples were collected throughout the sampling period, with a smaller peak in summer. Small numbers of Anopheles (Anopheles) pseudopunctipennis were found throughout the year. Relative humidity, with a 15-day delay, was the factor that most strongly contributed to the temporal sample fluctuation. We conclude that the best season for anopheline development in the study area is from spring to fall, although the period with the greatest transmission risk is the fall, with the greatest An. pseudopunctipennis abundance.

Species diversity and seasonal abundance of Culicoides biting midges in northwestern Argentina.

The species diversity and seasonal abundance of biting midges of the genus Culicoides (Diptera: Ceratopogonidae) were studied in northwestern Argentina during the period 2003-2005. A total of 5437 Culicoides specimens were collected using CDC light traps in three areas of the mountainous rainforest area. The most common species were Culicoides paraensis (Goeldi) and C. insignis Lutz, Culicoides lahillei (Iches), C. venezuelensis Ortiz & Mirsa, C. debilipalpis Lutz and C. crescentis Wirth & Blanton were also collected. Culicoides paraensis was abundant during the summer, and C. insignis and C. lahillei during late summer and early fall. Accumulated rainfall was the climatic variable most related to fluctuation in abundance of C. paraensis.

Impact of reduced endogenous anti-coagulation protein activity on vascular events of peripheral arterial disease.

AIM: Aim of the study is to elucidate the prevalence and the prognosis of patients with peripheral arterial disease (PAD) who have reduced endogenous anti-coagulation protein activity. METHODS: Ninety six patients with PAD were studied, including 45 patients with intermittent claudication and 51 with critical limb ischemia. Among them 65 patients underwent peripheral artery bypass grafting. Venous blood samples were obtained and plasma activity level of Protein C (PC), Protein S (PS), Plasminogen (PLG), Antithrombin (AT) were measured. Based on the patients' clinical database the prevalence and clinical relevance was studied. RESULTS: In our PAD patients PC activity is reduced in 18.8%, PS activity is reduced in 16.7%, PLG activity was reduced in 15.6% and AT activity was reduced in 24.0%. The incidence of AT activity deficiency was significantly higher in patients with critical limb ischemia than patients with claudication (P<0.01). After revascularization, arterial event free rate of patients with PC or PS activity deficiency and those with PLG deficiency were significantly lower than those without during the mean follow-up period of 26+/-31 months. The incidence of thromboembolic episodes and leg amputation rate were significantly worse in patients with PC deficiency. CONCLUSIONS: PAD patients with reduced endogenous anti-coagulation proteins show worse prognosis than those without. Surgeons must be aware of it to improve the outcome of arterial revascularization.

Mycobiota and aflatoxins in raw materials and pet food in Brazil.

Commercial feedstuffs are a basic element in modern pet husbandry in the world. In dogs, the effect of mycotoxins is severe and can lead to death. Few reports on the influence of dietary mycotoxins were found in the scientific literature. The aims of this work were to isolate and identify the mycoflora and to determine the aflatoxins (AFs) natural occurrence in raw materials and ready dry pet food. Therefore, the aflatoxigenic capacity of Aspergillus flavus species was investigated. Aspergillus was the prevalent genera (65-89%) followed by Penicillium and Fusarium spp. Aspergillus flavus was the most prevalent species, followed by Aspergillus sydowii, Aspergillus fumigatus and Aspergillus versicolor. Aspergillus flavus frequencies ranged from 58% to 86% except in sorghum meal. All samples assayed (except corn grains and ready pet food) showed Fusarium spp. contamination. Corn meal and corn meal and gluten samples had 100% Fusarium verticillioides. Fusarium graminearum was isolated from sorghum meal. Aspergillus flavus strains (75%) isolated from raw materials and 57% from pet food were able to produce AFs. All samples showed AFs contamination percentages over 70%; corn and sorghum meal obtained the highest AFs levels. Ready pet food did not show quantitative levels of the tested toxins. This is the first report of the aflatoxigenic capacity by A. flavus from Brazilian pet food.

Scale-up from shake flasks to fermenters in batch and continuous mode with Corynebacterium glutamicum on lactic acid based on oxygen transfer and pH.

Scale-up from shake flasks to fermenters has been hampered by the lack of knowledge concerning the influence of operating conditions on mass transfer, hydromechanics, and power input. However, in recent years the properties of shake flasks have been described with empirical models. A practical scale-up strategy for everyday use is introduced for the scale-up of aerobic cultures from shake flasks to fermenters in batch and continuous mode. The strategy is based on empirical correlations of the volumetric mass transfer coefficient (k(L) a) and the pH. The accuracy of the empirical k(L) a correlations and the assumptions required to use these correlations for an arbitrary biological medium are discussed. To determine the optimal pH of the culture medium a simple laboratory method based on titration curves of the medium and a mechanistic pH model, which is solely based on the medium composition, is applied. The effectiveness of the scale-up strategy is demonstrated by comparing the behavior of Corynebacterium glutamicum on lactic acid in shake flasks and fermenters in batch and continuous mode. The maximum growth rate (micro(max) = 0.32 h(-1)) and the oxygen substrate coefficient (Y O2 /S= 0.0174 mol/l) of C. glutamicum on lactic acid were equal for shake flask, fermenter, batch, and continuous cultures. The biomass substrate yield was independent of the scale, but was lower in batch cultures (Y(X/S) = 0.36 g/g) than in continuous cultures (Y(X/S) = 0.45 g/g). The experimental data (biomass, respiration, pH) could be described with a simple biological model combined with a mechanistic pH model.

An experimental comparison of respiration measuring techniques in fermenters and shake flasks: exhaust gas analyzer vs. RAMOS device vs. respirometer.

Respiration measurement is applied as a universal tool to determine the activity of biological systems. The measurement techniques are difficult to compare, due to the vast variety of devices and analytical procedures commonly in use. They are used in fields as different as microbiology, gene engineering, toxicology, and industrial process monitoring to observe the physiological activity of living systems in environments as diverse as fermenters, shake flasks, lakes and sewage plants. A method is introduced to determine accuracy, quantitation limit, range and precision of different respiration measurement devices. Corynebacterium glutamicum cultures were used to compare an exhaust gas analyzer (EGA), a RAMOS device (respiration measurement in shake flasks) and a respirometer. With all measuring devices it was possible to determine the general culture characteristics. The EGA and the RAMOS device produced almost identical results. The scatter of the respirometer was noticeably higher. The EGA is the technique of choice, if the reaction volume is high or a short reaction time is required. The possibility to monitor cultures simultaneously makes the RAMOS device an indispensable tool for media and strain development. If online monitoring is not compulsive, the respiration of the investigated microbial system extremely low, or the sample size small, a respirometer is recommended.

Metabolic activity of Corynebacterium glutamicum grown on L: -lactic acid under stress.

Respiration measurement in shake flasks is introduced as a new method to characterize the metabolic activity of microorganisms during and after stress exposure. The major advantage of the new method is the possibility to determine the metabolic activity independent of manual sampling without the necessity to change the culture vessel or the cultivation medium. This excludes stress factors, which may be induced by transferring the microorganisms to plates or respirometers. The negative influence, which interruptions of the shaker during sampling times may have on the growth of microorganisms was demonstrated. The applicability of the method was verified by characterizing the behavior of Corynebacterium glutamicum grown on the carbon source L: -lactic acid under stress factors such as carbon starvation, anaerobic conditions, lactic acid, osmolarity, and pH. The following conditions had no effect on the metabolic activity of C. glutamicum: a carbon starvation of up to 19 h, anaerobic conditions, lactic acid concentrations up to 10 g/l, 3-(N-morpholino) propanesulfonic acid buffer concentrations up to 42 g/l, or pH from 6.4 to 7.4. Lactic-acid concentrations from 10 to 30 g/l lead to a decrease of the growth rate and the biomass substrate yield without effecting the oxygen substrate conversion. Without adaptation, the organism did not grow at pH< or =5 or > or =9.

Intrapleural administration of a large amount of diluted fibrin glue for intractable pneumothorax.

OBJECTIVE: Pleurodesis using chemical agents has been applied to high-risk patients with pneumothorax. This treatment, however, is sometimes unsuccessful in patients with intractable pneumothorax or intrapleural dead space. We developed a technique for the intrapleural administration of diluted fibrin glue as a treatment for such patients. METHODS: Fibrin glue was diluted fourfold with saline solution and/or contrast medium. Pleurodesis with a large amount of the diluted fibrin glue was performed in 40 high-risk patients with intractable pneumothorax and in 13 postthoracotomy patients with persistent air leakage associated with an intrapleural dead space. RESULTS: The air leaks were stopped by administration of the glue in all patients of both groups. During the follow-up period, a recurrence rate of 12.5% was observed in the former group. These recurrent pneumothoraces also were successfully treated by glue administration with no further recurrence. In the 13 postthoracotomy patients, there was no recurrence after the initial treatment. Pyrexia (12.5%) and chest discomfort (4.1%) were observed as side effects, but there were no findings of severe chest pain or thoracic empyema. CONCLUSIONS: These results suggest that intrapleural administration of a large amount of diluted fibrin glue is a useful treatment for intractable pneumothoraces in high-risk or postthoracotomy patients who have an intrapleural dead space.

[Self-expandable metallic stent therapy for inferior vena cava obstruction secondary to malignancy: clinical observations].

To evaluate the self-expandable metallic stent therapy for inferior vena caval obstruction (IVCO) secondary to malignant liver tumors, changes in caval pressure, the symptoms and hemobiochemical values were observed. Among 16 IVCO cases with higher caval pressure than 20 cmH2O at the peripheral caval lumen to the stenosis, nine cases consisting of five extracaval compression cases and four intravenous tumor thrombi cases subjected the stent therapy. Other three subjected radiotherapy and the other four cases inactive supportive care. Immediately after the Z-stent implantation, the averaged caval pressure distal to the stenosis decreased from 27.7 +/- 3.5 cmH2O to 14.7 +/- 2.6 cmH2O. One case developed 8 cmH2O increase of right atrial pressure but no lung edema. The urine excretion volume increased after stent. The decrease in caval pressure correlated with the urine volume of the day after the stenting (gamma = 0.83), symptomatic improvements of leg edema (gamma = 0.68), ascites (gamma v 0.51) and scrotal edema (gamma = 0.70). Five cases showed gradual increase in platelet number. All elevated LDH and elevated fibrinogen value decreased. These changes would suggest physiologic benefits of the IVC stent therapy. Compression cases showed better improvements and courses than the thrombi cases. Two thrombi cases endured severe conditions suspected of triggered by the procedure. Conclusively, the stent therapy to the IVC obstruction was thought to effect hemodynamically and hematobiochemically.

[Expandable metallic stent therapy for SVC syndrome--effects on local venous pressure, vascular diameter, symptoms, and these correlations].

To evaluate the efficacy of Z-stent therapy for SVC syndrome, we studied changes in the pressure, the diameter of stenotic lumen and the symptoms in the cases of SVC syndrome with higher pressure than 30 cmH2O at distal to the stenosis. The symptoms were classified and graded to be scored up. Immediately after the Z-stent placement into the stenotic lesions, the venous pressure distal to the stenosis decreased from 36.0 +/- 3.4 cmH2O to 12.0 +/- 12.0 cmH2O (p < 0.001), the diameter of stenotic lumen increased from 3.3 +/- 3.4 mm to 14.0 +/- 3.4 mm (p < 0.01). According to the remarkable symptomatic improvements the averaged score decreased from 6.7 to 1.3 (p < 0.01). The pressure, the diameter and the symptom scores were highly correlated each other (magnitude of gamma not equal to 0.9). Among two cases with the right atrial pressure increase by 2 cmH2O after the placement one suffered transient cardiac in compensation due to overload by reperfusion. Conclusively, the Z-stent therapy was very effective on the SVC syndrome in reducing abnormally elevated venous pressure due to the stenosis, and relieving the symptoms, while the pressure monitor was necessary.

An immunogenetically defined and immunodominant Trypanosoma cruzi antigen.

Two strains of mice, A. SW (H-2s) and A.CA (H-2f), were immunized with live trypomastigotes or epimastigotes of the Tulahuen strain of Trypanosoma cruzi or with their sonicates. By immunowestern blotting, sera from A.SW mice, but not from A.CA, recognized, in an immunodominant fashion, a 45 kDal polypeptide (Tc45) present in both epimastigotes and trypomastigotes. Since A.SW and A.CA strains are congenic for the major histocompatibility H-2 complex, recognition of Tc45 seems to be controlled by this genetic region or by gene(s) located in its immediate vicinity. Subcellular fractionation revealed that Tc45 is mainly present at the cytoplasmic compartment.

Sr and Ba transients in isolated snail neurones studied with fura-2. The recovery from depolarization induced load and modulation of Ca release from intracellular stores.

The fluorescent Ca-sensitive probe fura-2 was used in isolated non-identified neurons of the snail, Helix pomatia, to study the recovery from Sr and Ba loading and the effect of these cations on Ca-induced Ca release. Sr was shown to behave similarly to Ca, whereas Ba ions were not sequestered within the cell. Intracellular Ba blocked both the voltage-gated channels in the plasma membrane and the Ca release channels in the membrane of intracellular stores.

Non-lytic antibodies in H-2-controlled resistance to acute infection with Trypanosoma cruzi.

1. Resistance to acute Trypanosoma cruzi infection in mice is a polygenic character with a major factor linked to the murine major histocompatibility system (H-2). We found that F1 hybrids A.CA(H-2f)/B10.Br(H-2k) between two susceptible strains are strongly resistant. 2. Resistant B10(H-2b) and A.SW(H-2s) animals survived 60 or more days after an intraperitoneal injection of 10(4) Tulahuén strain blood trypomastigotes. The specific antibody response of these individuals increased continuously up to 100 days or more. Parasitemia reached a peak at day 8 in all strains. Thereafter, the number of blood parasites in resistant animals showed an irregular but persistent decrease. 3. Susceptible congenic B10.Br and A.CA animals showed lower levels of specific anti-T. cruzi antibodies and an increase in parasitemia until death. B10.Br mice died 14 to 20 days after infection. A.CA animals were extremely susceptible, showing a sharp and sustained increase in parasitemia starting on day 12, followed by death no later than day 15 post-inoculation. 4. We found a significant correlation between IgG levels present in serum of resistant mice from 20 days on and protection against acute death. Whole immune anti-T. cruzi serum or its purified IgG class fraction neutralized T. cruzi inocula in vitro as shown by a significantly increased survival of recipient susceptible A.CA mice. 5. This IgG protective effect is independent of the protective effect mediated by the terminal activation of the complement cascade, since the parasites were inoculated with heat-inactivated immune sera and both recipient (A.CA) and donor (A.SW) strains lack C5.