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The portable chlorophyll meter (SPAD-502) has been successfully used for a rapid and direct estimation of total chlorophyll content (TCHL) in the leaves of some crops. In this work, SPAD-502 meter readings and TCHL concentration were compared for the leaves of Amaranthus vlitus L., a common weed. SPAD readings were linearly and positively correlated to TCHL concentration in the leaves. A linear correlation was also shown between SPAD-502 readings and some physiological parameters of the leaves, such as photosynthesis, transpiration, and stomatal conductance. [ABSTRACT FROM AUTHOR]

Gut regulatory peptides bombesin (BBS) and neurotensin (NT) exert a wide spectrum of biological actions on gastrointestinal tissues and researchers have previously shown that they improve intestinal barrier function and oxidative stress in experimentally jaundiced rats. In the present study, we explored their potential action on liver histology and oxidative status in bile duct ligated rats. direct inhibitor of NF-kB, had any effect on this lack of apoptotic response to TGF-b when the complete medium was present observed in neoplastic tumours. Researchers have found that TGF-b induced cell-cycle arrest in all types of cultures independently of the tumoral origin hyperplastic, neoplastic or metastatic. This result was in contrast with results reported for other epithelial tumours.

Light intensity and wind are critical environmental factors of abiotic stress on plants, triggering a considerable number of morphological and physiological responses. This study tested the hypothesis that different light and wind conditions (full sunlight ± wind, shade ± wind) would affect the leaf content of photosynthetic pigments and anthocyanins, as well as the plant height, the fresh and dry weight of the aboveground part, and Water-Use Efficiency on Ocimum basilicum plants. About 16 days after the application of the different conditions, all leaf pigments of the shaded plants exhibited increased contents compared to the lightened ones. Subsequently, this response was enhanced until the 39th day, which was the final day of the experiment. Furthermore, shaded plants grew taller, although their fresh and dry weight and Water-Use Efficiency were lower than that of the corresponding lightened ones. On the other hand, wind did not have any effect on pigment content. Concerning the plant growth indexes, reduced values were observed on the wind-treated plants. The above results demonstrate a considerable effect of light intensity while the applied wind seems to be mild enough to induce important plant responses, partially confirming the hypothesis studied.

In the intricate landscape of multiple myeloma, a hematologic malignancy of plasma cells, bone disease presents a pivotal and often debilitating complication. The emergence of Chimeric Antigen Receptor T-cell (CAR-T) therapy has marked a pivotal shift in the therapeutic landscape, offering novel avenues for the management of MM, particularly for those with relapsed or refractory disease. This innovative treatment modality not only targets malignant cells with precision but also influences the bone microenvironment, presenting both challenges and opportunities in patient care. In this comprehensive review, we aim to examine the multifaceted aspects of bone disease in patients with multiple myeloma and concurrent CAR-T therapy, highlighting its clinical ramifications and the latest advancements in diagnostic modalities and therapeutic interventions. The article aims to synthesize current understanding of the interplay between myeloma cells, CAR-T cells, and the bone microenvironment in the context of current treatment strategies in this challenging and unique patient population., Competing Interests: Declaration of Competing Interest None of the authors have any conflicts of interest to disclose., (Copyright © 2024. Published by Elsevier B.V.)

Primary bone malignancies, including osteosarcoma (OS), are rare but aggressive. Current OS treatment, involving surgical resection and chemotherapy, has improved survival for non-metastatic cases but remains ineffective for recurrent or metastatic OS. Oncolytic viral therapy (OVT) is a promising alternative, using naturally occurring or genetically modified viruses to selectively target and lyse cancer cells and induce a robust immune response against remaining OS cells. Various oncolytic viruses (OVs), such as adenovirus, herpes simplex virus, and measles virus, have demonstrated efficacy in preclinical OS models. Combining OVT with other therapeutics, such as chemotherapy or immunotherapy, may further improve outcomes. Despite these advances, challenges in reliability of preclinical models, safety, delivery, and immune response must be addressed to optimize OVT for clinical use. Future research should focus on refining delivery methods, exploring combination treatments, and clinical trials to ensure OVT's efficacy and safety for OS. Overall, OVT represents a novel approach with the potential to drastically improve survival outcomes for patients with OS.

Purpose of Review: This review summarizes current findings regarding limb amputation within the context of cancer, especially in osteosarcomas and other bony malignancies. We seek to answer the question of how amputation is utilized in the contemporary management of cancer as well as explore current advances in limb-sparing techniques., Recent Findings: The latest research on amputation has been sparse given its extensive history and application. However, new research has shown that rotationplasty, osseointegration, targeted muscle reinnervation (TMR), and regenerative peripheral nerve interfaces (RPNI) can provide patients with better functional outcomes than traditional amputation. While limb-sparing surgeries are the mainstay for managing musculoskeletal malignancies, limb amputation is useful as a palliative technique or as a primary treatment modality for more complex cancers. Currently, rotationplasty and osseointegration have been valuable limb-sparing techniques with osseointegration continuing to develop in recent years. TMR and RPNI have also been of interest in the modern management of patients requiring full or partial amputations, allowing for better control over myoelectric prostheses., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Leaf wounding is a common stress that triggers a great number of plant mechanisms, while the overall plant status and age could also be critical for these mechanisms. However, there are not sufficient data about plants' physiological responses after leaf wounding that has been imposed at different developmental stages. In this study, physiological parameters, such as photosynthesis, transpiration, and stomatal conductance, as well as the chlorophyll and anthocyanin leaf contents, of Ocimum basilicum var. minimum L. plants were measured for seven days on wounded plants during three different developmental stages (vegetative, budding, and flowering). All of the measurements were conducted on control and wounded plants, while on the latter they were conducted on both wounded and intact leaves. The physiological parameters mentioned above revealed a remarkable decrease in wounded leaves of the budding and flowering plants, while they seemed to be only partially affected on the leaves of vegetative plants. The physiological parameters' decrease was not only an immediate plant response that was observed 1-2 h after wounding, but, in general, it was constant (during the seven days of treatments) and diurnal (from 8 a.m. to 8 p.m.). The wounded leaves revealed an immediate and constant anthocyanin content decrease during all of the developmental stages, while the corresponding chlorophyll decrease was mainly evident in the flowering plants. Regarding the intact leaves, they exhibited, in general, a similar profile to that of the control ones. The results above reveal that at the vegetative stage, basil plants are more tolerant to leaf wounding than those at the budding and flowering stages, implying that the plant's response to wounding is a phenomenon that depends on the plant's developmental stage.

The investigation about the leaf wounding effect on plant physiological procedures and on leaf pigments content will contribute to the understanding of the plants' responses against this abiotic stress. During the experiment, some physiological parameters such as photosynthesis, transpiration and stomatal conductance as well as the chlorophyll and anthocyanin leaf contents of Ocimum basilicum , Salvia officinalis, and Mentha piperita plants were measured for about 20-40 days. All the measurements were conducted on control and wounded plants while in the latter, they were conducted on both wounded and intact leaves. A wide range of responses was observed in the wounded leaves, that is: (a) immediate decrease of the gas exchange parameters and long-term decrease of almost all the measured variables from O. basilicum , (b) immediate but only short-term decrease of the gas exchange parameters and no effect on pigments from M. piperita , and (c) no effect on the gas exchange parameters and decrease of the pigments content from S. officinalis . Regarding the intact leaves, in general, they exhibited a similar profile with the control ones for all plants. These results imply that the plant response to wounding is a complex phenomenon depending on plant species and the severity of the injury.

Cyclic nucleotide phosphodiesterases (PDE) break down cyclic nucleotides such as cAMP and cGMP, reducing the signaling of these important intracellular second messengers. Several unique families of phosphodiesterases exist, and certain families are clinically important modulators of vasodilation. In the current work, we have summarized the body of literature that describes an emerging role for the PDE4 subfamily of phosphodiesterases in malignancy. We have systematically investigated PDE4A, PDE4B, PDE4C, and PDE4D isoforms and found evidence associating them with several cancer types including hematologic malignancies and lung cancers, among others. In this review, we compare the evidence examining the functional role of each PDE4 subtype across malignancies, looking for common signaling themes, signaling pathways, and establishing the case for PDE4 subtypes as a potential therapeutic target for cancer treatment.

Background: Thromboelastography has called into question the coagulopathy seen following partial hepatectomy. However the coagulation profile in cirrhotic livers has not been studied. Our objective was to determine the coagulation profile following partial hepatectomy in normal and cirrhotic livers., Methods: Patients undergoing liver resection were prospectively enrolled in the study. The prothrombin time and international normalized ratio, as well as the thromboelastogram, were obtained preoperatively, post-operatively, and on post-operative days 1, 3, and 5., Results: 22 noncirrhotic and 11 cirrhotic patients undergoing liver resection were enrolled. Postoperatively the thromboelastogram demonstrated a hypercoagulable profile in 64%, 33%, 39% and 36% of patients on post-operative days 0, 1, 3 and 5 respectively. There was no difference between patients with cirrhosis and those without underlying liver disease., Conclusion: Patients appear to have a similar coagulation profile after liver resection regardless of underlying cirrhosis with many having a hypercoagulable profile., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Plant catalases exhibit spatial and temporal distribution of their activity. Moreover, except from the typical monofunctional catalase, a bifunctional catalase-peroxidase has been reported. The aim of this study was to investigate whether the leaf and root catalases from six different plant species ( Lactuca sativa , Cichorium endivia , Apium graveolens , Petroselinum crispum, Lycopersicon esculentum , and Solanum melongena ) correspond to the monofunctional or the bifunctional type based on their sensitivity to the inhibitor 3-amino-1,2,4-triazole (3-AT). The leaf catalases from all species seem to be monofunctional since they are very sensitive to 3-AT. On the other hand, the root enzymes from Lactuca sativa , Cichorium endivia , Lycopersicon esculentum , and Solanum melongena seem to be bifunctional catalase-peroxidases, considering that they are relatively insensitive to 3-AT, whereas the catalases from Apium graveolens and Petroselinum crispum display the same monofunctional characteristics as the leaves' enzymes. The leaf catalase activity is usually higher ( Lactuca sativa , Petroselinum crispum , and Solanum melongena ) or similar ( Cichorium endivia and Apium graveolens ) to the root one, except for the enzyme from Lycopersicon esculentum , while in all plant species the leaf protein concentration is significantly higher than the root protein concentration. These results suggest that there are differences between leaf and root catalases-differences that may correspond to their physiological role., Competing Interests: The authors declare no conflict of interest.

Several options exist to palliate malignant obstruction (MBO), none of which have established consensus among surgeons. The purpose of this study was to establish outcomes of diverting stoma (DS), internal bypass (IB), and palliative resection (PR) for a tertiary academic referral surgical oncology service. All patients presenting to a surgical oncology service with malignant bowel obstruction over a 3-year period were identified. Records were reviewed to determine success of diversion, bypass, or resection and associated cost, length of stay (LOS), morbidity, and mortality. Forty-three patients undergoing palliative surgery were identified. The success of each approach was 80, 78, and 63 per cent for diversion, bypass, and resection, respectively. Major morbidity (63%), mortality (16%), and LOS (26 days) were greatest in those undergoing PR, but so was survival (8.4 months). DS and IB had comparable morbidity (40 and 33%), mortality (10 and 0%), and LOS (25 and 21 days), but survival was shorter for DS (5.3 vs 6.5 months). Cost of PR was significantly greater ($79,000) than both DS ($36,000) and IB ($51,000). Escalation in complexity of palliative measures for MBO results in improved survival but at significant cost both economically and physiologically. Quality of life should be discussed with patients when deciding how best to palliate their symptoms.

Objective: The aim of this study was to measure the production of superoxide radical (O2-), a direct indicator of oxidative stress, in 4 vital organs of rats subjected to hemorrhagic shock. For this purpose, and for the first time, a new quantitative assay for the ex vivo measurement of O2- via an established 1:1 molar relationship between O2- and 2-OH-ethidium was used. The production of lipid hydroperoxides (LOOHs), a standard method of evaluation of oxidative stress, was also used for reasons of comparison., Methods: Sixteen male Wistar rats were divided into 2 groups: sham and hemorrhagic shock, targeting to a mean arterial pressure of 30 to 40 mm Hg for 60 minutes. Three hours after resuscitation, tissues were collected for measurement of LOOHs and O2- production., Results: Hemorrhagic shock induced increased production of LOOHs in the gut, liver, and lungs (P<.001), whereas the production of O2- was also increased in the gut (P<.001), liver (P<.001), and, to a lesser extent, in the lungs (P<.05). The oxidative load of the kidneys, as estimated by both techniques, remained unaffected., Conclusion: The results of this new O2- assay were comparable with the results of the established LOOHs method, and this assay proved to be accurate and sensitive in the detection and quantification of O2- production in all organs tested. Thus, the proposed direct measurement of O2- in critically ill patients often facing in extremis situations could be used as a prognostic tool and as a method to evaluate therapeutic interventions in the setting of emergency medicine., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objectives: To study the effect of clonidine pre-treatment on hemorrhagic shock (H/S)-induced endotoxemia and oxidative stress (OS) in three vital organs of the rat., Methods: The study protocol consisted of two arms: one for the measurement of organic hydroperoxide (LOOH) and superoxide radical (O(2)(-·)) production in the gut, liver, and lungs (n = 32 rats) and one for the measurement of endotoxin in portal and systemic circulation (n = 32 rats). Four animal groups (sham, clonidine, H/S, and clonidine-H/S group) were used in each arm. Three hours after H/S and concominant blood resuscitation, tissues were collected for LOOHs and O(2)(-·) measurement and blood samples were obtained for endotoxin determination., Results: Clonidine pre-treatment prior to H/S resulted in a significant reduction of LOOHs and O(2)(-·) production in all vital organs (P < 0.05-0.001), while additionally, clonidine reduced H/S-induced endotoxemia in portal (P < 0.05) and systemic circulation as well (P < 0.01)., Discussion: Clonidine pre-treatment prevents endotoxemia and OS in the gut, liver, and lungs of rats subjected to severe H/S. The improved intestinal barrier function probably stems from the antioxidant effect of clonidine on the intestinal epithelium, whereas the reduced endotoxemia may contribute to a decreased OS observed in the liver and lungs.

We investigated the mechanism of Coomassie brilliant blue G-250 (CBB) binding to proteins in order to develop a protein assay with the maximum possible sensitivity. We found that the neutral ionic species of CBB binds to proteins by a combination of hydrophobic interactions and heteropolar bonding with basic amino acids. On the basis of these findings, we developed a very sensitive hydrophobic assay for proteins (at the nanogram level) using the hydrophobic reagents ammonium sulfate and trichloroacetic acid under pH conditions that increase neutral species concentration in the assay reagent in order to enhance the binding of more CBB dye molecules per protein molecule than in previous CBB-based assays.

Oxidative stress seems to be a cardinal feature of cholestasis, implicated in the pathophysiology of organ injury not only in the liver, but also in several extrahepatic tissues. The present study was designed to assess directly oxidative stress in vital organs of experimentally jaundiced rats by measuring the key oxidative stress marker superoxide radical (O2(*-)). Twelve male Wistar rats underwent laparotomy and were divided into two groups - group I (n = 6) sham operated, and group II (n = 6) bile-duct ligated. Ten days later, the O2(*-) formation rate was quantified in liver, intestine, kidney and heart of all animals. These measurements were done by application of a new ultrasensitive fluorescent assay for the in vivo quantification of O2(*-), which is based on the 1:1 molar stoichiometric reaction of O2(*-) with dihydroethidine (DHE, an O2(*-) trap) that results in the formation of the specific product 2-OH-ethidium. 2-OH-Ethidium was measured by fluorescence in rats' organs and its formation rate was converted to O2(*-) production rate. As compared to sham-operated rats, in jaundiced rats there was a significant increase of O2(*-) in the intestine (136%, P < 0.01), liver (104%, P < 0.01), and kidney (95%, P < 0.01), whereas there was no significant difference in heart O2(*-) levels. Superoxide radical may play an important role in the pathophysiology of cholestatic liver injury, intestinal barrier failure and renal failure, associated with postoperative morbidity and mortality in obstructive jaundice. On the contrary, O2(*-) and oxidative stress are possibly not implicated in the pathophysiology of hepatic cardiomyopathy.

Sclerotium-forming filamentous fungi are of great agricultural and biological interest because they can be viewed as models of simple metamorphosis. They differentiate by asexually producing sclerotia but the processes involved in sclerotial metamorphosis were poorly understood. In 1997, it was shown for the first time that the sclerotial differentiation state in Sclerotium rolfsii concurred with increasing levels of lipid peroxides. This finding prompted the development of a theory supporting that sclerotial metamorphosis is induced by oxidative stress. Growth factors that reduce or increase oxidative stress are expected to inhibit or promote sclerotium metamorphosis, respectively. This theory has been verified by a series of published data on the effect of certain hydroxyl radical scavengers on sclerotial metamorphosis, on the identification and quantification of certain endogenous antioxidants (such as ascorbic acid, β-carotene) in relation to the fungal undifferentiated and differentiated states, and on their inhibiting effect on sclerotial metamorphosis as growth nutrients. In 2004-2005, we developed assays for the measurement of certain redox markers of oxidative stress, such as the thiol redox state, the small-sized fragmented DNA, and the superoxide radical. These new advances allowed us to initiate studies on the exact role of glutathione, hydrogen peroxide, and superoxide radical on sclerotial metamorphosis. The emerging data, combined with similar data from other better-studied fungi, allowed us to make some preliminary postulations on the ROS-dependent biochemical signal transduction pathways in sclerotiogenic filamentous fungi.

Purpose: In the present study, we examined the effects of pentylenetetrazol (PTZ) administration on the thiol redox state (TRS), lipid peroxidation, and protein oxidation in the mouse striatum to (a) quantitate the major components of TRS and relate them to oxidative stress, and (b) investigate whether neuronal activation without synchronization, induced by subconvulsive doses of PTZ, can cause similar qualitative effects on TRS in this brain area. Specifically, we examined the TRS components glutathione (GSH), glutathione disulfide (GSSG), cysteine (CSH), protein thiols (PSH), and the protein (P) and nonprotein (NP/R) disulfides PSSR, NPSSR, NPSSC, and PSSP., Methods: TRS components were measured photometrically (GSSG enzymatically) as were lipid peroxidation and protein oxidation., Results: GSH, GSSG, and NPSSC levels are decreased by 45%, 38% and 26%, respectively, at 15 min after seizure; PSSP and PSSR levels and lipid peroxidation are increased by 47%, 200% and 22%, respectively, whereas CSH, NPSSR, PSH, PSSC, and protein carbonyl levels do not change. At 30 min after seizure, GSH, GSSG, CSH, NPSSC, and protein carbonyl levels are decreased by 26%, 62%, 25%, 40%, and 13%, respectively. PSSP and NPSSR levels are increased by 30% and 42%, respectively, whereas PSH, PSSC, PSSR, and lipid peroxidation remain unchanged. At 24 h after seizure, GSH, NPSSR, PSSR, and lipid-peroxidation levels return to normal; GSSG, CSH, NPSSC, and protein carbonyl levels are decreased by 44%, 22%, 30%, and 27%, respectively., Conclusions: The significant decrease in GSH, GSSG, CSH, and NPSSC and the increase in PSSP, NPSSR, PSSR, and lipid peroxidation after PTZ-induced seizure strongly suggest increased oxidative stress in the mouse striatum.

In this study we measured thiol redox state (TRS) and the oxidative stress indicator lipid peroxidation in midbrain and striatum of adult (4 months old) male control (+/+) and weaver (wv/wv) mice in order to relate them with oxidative stress in conditions of progressive and severe (approximately 70%) nigrostriatal dopaminergic neurodegeneration. Specifically, we measured the specific TRS components glutathione (GSH), glutathione disulfide (GSSG), cysteine (CSH), and the general classes of TRS components. The latter are the protein thiols (PSH) and the disulfides between (a) protein (P) and protein thiols (PSSP), (b) protein and non-protein (NP/R) thiols (PSSR, PSSC) and (c) non-protein and non-protein thiols (NPSSR, NPSSC). In addition, the main product of lipid peroxidation malonyl dialdehyde (MDA) was estimated. In the midbrain of wv/wv, GSH and NPSSC levels are decreased (44% and 64%, respectively) and GSSG, NPSSR, CSH, PSH, PSSP, PSSR and MDA levels are increased (23%, 660%, 110%, 51%, 68%, 18% and 44%, respectively). In the striatum of male wv/wv, protein and non-protein thiol/disulfide and MDA levels do not change, possibly due to the high decrease in striatal dopamine level versus midbrain. Our data show that the high degeneration of the dopaminergic nigrostriatal neurons in male adult wv/wv mice is accompanied by significant changes in TRS and an increase in lipid peroxidation in the midbrain, suggesting involvement of oxidative stress in the degeneration of dopaminergic neurons. They also strengthen the possible use of thiol antioxidants for the development of new neuroprotective therapeutic strategies for neurodegenerative diseases, such as Parkinson's disease.

Objective: To evaluate the effect of bombesin (BBS) and neurotensin (NT) on intestinal histopathology, intestinal oxidative stress, and endotoxemia in experimental obstructive jaundice., Summary Background Data: Obstructive jaundice compromises gut barrier function, resulting in endotoxemia. BBS and NT, exerting various biologic actions on gastrointestinal tissues, preserve gut mucosal integrity in cases of injury or atrophy., Methods: Seventy male Wistar rats were randomly divided into 5 groups: I = controls, II = sham operated, III = bile duct ligation (BDL), IV = BDL + BBS (30 microg/kg/d), V = BDL + NT (300 microg/kg/d). By the end of the experiment, on day 10, endotoxin was measured in portal and aortic blood. Tissue sections of the terminal ileum were examined histologically, and villus density, mucosal thickness, mitotic activity and apoptosis in crypts were assessed. In addition, ileal mucosa was analyzed for DNA and protein content. To estimate intestinal oxidant/antioxidant equilibrium, lipid peroxidation, protein oxidation, and thiol redox state (reduced glutathione [GSH], oxidized glutathione [GSSG], total nonprotein mixed disulfides [NPSSR], protein thiols [PSH], and protein disulfides [PSSP]) were determined on tissue homogenates from the terminal ileum., Results: BBS or NT administration significantly reduced portal and systemic endotoxemia observed in obstructive jaundice. Both factors reversed obstructive jaundice-induced morphologic features of intestinal atrophy, increasing villus density and mucosal thickness. This effect was accompanied by induction of mitoses and reduction of apoptosis in intestinal crypts. Mucosal DNA and protein content were reduced, although not to significant levels, in BDL animals and restored to control levels after BBS or NT treatment. Moreover, BBS or NT administration protected the intestine in jaundiced rats against oxidative stress, as demonstrated by reduction of intestinal lipid peroxidation, increase of the antioxidant GSH, and decrease of the oxidized forms GSSG and NPSSR, while BBS additionally reduced protein oxidation as well., Conclusions: Administration of BBS or NT in bile duct-ligated rats exerts beneficial effects on intestinal oxidative stress, cell proliferation, apoptosis, and endotoxemia. This observation might be of potential value in patients with extrahepatic cholestasis.

In the present study we examined the effects of pentylenetetrazol (PTZ) administration on the thiol redox state (TRS), lipid peroxidation and protein oxidation in left and right mouse cerebral cortex in order (a) to quantitate the major components of the thiol redox state and relate them with oxidative stress and cortical laterality, and (b) to investigate whether neuronal activation without synchronization, induced by subconvulsive doses of PTZ, can cause similar qualitative effects on the thiol redox state. Specifically, we examined the TRS components [glutathione (GSH), glutathione disulfide (GSSG), cysteine (CSH), protein (P) thiols (PSH) and protein and non-protein (NP) mixed/symmetric disulfides (PSSR, NPSSR, NPSSC, PSSP)]. At 15 min after seizure, GSH, GSSG, CSH, NPSSC, PSSR and PSSC levels are decreased in left (14-50%) and right (11-53%) cortex while PSSP levels are increased in both left (1400%) and right (1600%) cortex. At 30 min after seizure, GSSG, CSH, NPSSC, PSSR and PSSC levels are decreased in left (14-51%) and right (18-56%) cortex while PSSP and protein carbonyl levels are increased in left (2300% and 20%, respectively) and right (2800% and 21%, respectively) cortex. At 24 h after seizure, the TRS components return to normal and protein carbonyl levels are decreased in left (16%) and right (20%) cortex. The significant decrease in GSH, GSSG, CSH, NPSSC, PSSR and PSSC, as well as the increase in protein carbonyl and the high increase in PSSP levels after PTZ-induced seizure indicate increased oxidative stress in cerebral cortex of mice, and of similar magnitude and TRS-component profiles between left and right cerebral cortex.

Gut regulatory peptides bombesin (BBS) and neurotensin (NT) exert a wide spectrum of biological actions on gastrointestinal tissues and we have previously shown that they improve intestinal barrier function and oxidative stress in experimentally jaundiced rats. In the present study, we explored their potential action on liver histology and oxidative status in bile duct ligated rats. Seventy male Wistar rats were randomly divided into five groups: controls, sham operated, bile duct ligated (BDL), BDL + BBS (10 microg/kg, s.c. x3), BDL + NT (300 microg/kg, i.p.). At the end of the experiment, on day 10, serum total bilirubin and alanine aminotransferase (ALT) levels were determined and endotoxin was measured in portal and aortic blood. Liver tissue samples were examined histologically for evaluation of the ratio of portal tracts presenting changes of obstructive cholangiopathy and neutrophils' number in portal tracts. In addition, hepatic oxidative status was estimated on liver homogenates by measurements of lipid peroxidation (malondialdehyde), protein oxidation (protein carbonyl groups) and thiol redox state [reduced glutathione (GSH), oxidized glutathione (GSSG), total non-protein mixed disulfides (NPSSR) and protein thiols (PSH)]. Administration of BBS or NT significantly reduced portal and aortic endotoxaemia observed in obstructive jaundice. Both agents significantly ameliorated liver injury, as demonstrated by improvement of obstructive cholangiopathy and reduction of ALT. This effect was accompanied by prevention of lipid peroxidation, protein oxidation and decrease of the oxidized forms GSSG and NPSSR. Moreover, neutrophil accumulation in portal tracts was significantly decreased. In conclusion, this study shows that gut regulatory peptides BBS and NT reduce cholestatic liver injury, exerting protective effects on portal tract architecture, neutrophil infiltration and hepatic oxidative stress in bile duct ligated rats.

In this study we evaluated oxidative stress (lipid peroxidation and protein oxidation) and thiol redox state [TRS: glutathione (GSH), glutathione disulfide (GSSG), cysteine (CSH), protein (P) thiols (PSH) and protein and non-protein (NP) mixed/symmetric disulfides (PSSR, NPSSR, NPSSC, PSSP)] in hippocampus after pentylenetetrazol (PTZ) administration at convulsive and subconvulsive dose. The significant decrease in PSH, CSH and NPSSC, as well as the increase in PSSP, NPSSR, lipid peroxidation and protein oxidation levels after PTZ-induced seizure indicate increased oxidative damage in hippocampus, although the levels of GSH and GSSG do not change significantly.

Sclerotinia minor accumulates beta-carotene at levels dependent upon oxidative growth conditions and differentiation. Beta-carotene accumulation is 2.5-fold higher in differentiated mycelia at high than at low oxidative stress, and approx. 3-fold higher in differentiated than in undifferentiated mycelia. It is proposed that beta-carotene may be produced by the fungus to counteract oxidative stress that develops during growth. This is shown by the finding that exogenous beta-carotene at growth non-inhibiting concentrations causes a concentration-dependent reduction of oxidative stress (lipid and protein peroxidation) and sclerotial differentiation in this fungus. The data of this study support our hypothesis that sclerotial differentiation in phytopathogenic fungi may be induced by oxidative stress.

Certain phytopathogenic fungi differentiate by forming sclerotia by an unclear biochemical mechanism. We have proposed that sclerotial differentiation might be regulated by fungal antioxidant defense. Part of this defense might be ascorbic acid, which in its reduced form is a well-known antioxidant. This natural antioxidant was studied in Sclerotium rolfsii in relation to oxidative-growth conditions, developmental stages and strain-differentiating ability. The transition of a sclerotial strain from the undifferentiated to the differentiated stage was accompanied by a sharp shift in the ratio of reduced/oxidized ascorbate toward the oxidized form. Ascorbate profiles and lipid peroxidation levels were different between the sclerotial strain grown under high- and low-oxidative stress conditions, as well as between a nonsclerotial S. rolfsii strain grown under high-oxidative stress conditions. In addition, the ratio of reduced/oxidized ascorbate in the nonsclerotial strain remained unchanged throughout growth. Lipid peroxidation under high-oxidative stress conditions in sclerotial S. rolfsii colonies one day before differentiation was 3.6-fold higher than in same-day colonies of this strain grown under low-oxidative stress conditions and 2.5-fold higher than in similar-day colonies of the nonsclerotial strain grown under high-oxidative stress conditions. Exogenous ascorbate caused a concentration-dependent reduction of lipid peroxidation and a proportional inhibition of the degree of sclerotial differentiation in the sclerotial strain grown under high-oxidative stress conditions by lowering its lipid peroxidation before differentiation to levels similar to the strain grown under low-oxidative stress conditions and to the nonsclerotial strain. Ascorbic acid might be produced by the sclerotial strain to reduce oxidative stress, although less efficiently than the nondifferenting strain. The data of this study support our theory that oxidative stress might be the triggering factor of sclerotial differentiation in phytopathogenic fungi.

The fungus Sclerotium rolfsii produces beta-carotene, the main detected carotenoid, in levels dependent upon oxidative growth conditions and upon differentiation. beta-Carotene accumulation is 5-, 6.5-, and 6.7-fold higher in undifferentiated mycelia, sclerotia, and differentiated mycelia, respectively, at high than at low oxidative stress. It accumulates more in older than in younger mycelia and is 2-fold higher in differentiated than in undifferentiated mycelia. We propose that beta-carotene is formed possibly to help the fungus reduce oxidative stress that develops during growth. This is supported by the finding that exogenous beta-carotene at non-growth-inhibiting concentrations causes a concentration-dependent reduction of oxidative stress (lipid peroxidation) of undifferentiated mycelia, which results in an equally proportional reduction of sclerotial differentiation. The data of this study support our hypothesis that sclerotial differentiation is induced by oxidative stress., (Copyright 2001 Academic Press.)