Oxidative Stress in Military Missions-Impact and Management Strategies: A Narrative Analysis.

This narrative review comprehensively examines the impact of oxidative stress on military personnel, highlighting the crucial role of physical exercise and tailored diets, particularly the ketogenic diet, in minimizing this stress. Through a meticulous analysis of the recent literature, the study emphasizes how regular physical exercise not only enhances cardiovascular, cognitive, and musculoskeletal health but is also essential in neutralizing the effects of oxidative stress, thereby improving endurance and performance during long-term missions. Furthermore, the implementation of the ketogenic diet provides an efficient and consistent energy source through ketone bodies, tailored to the specific energy requirements of military activities, and significantly contributes to the reduction in reactive oxygen species production, thus protecting against cellular deterioration under extreme stress. The study also underlines the importance of integrating advanced technologies, such as wearable devices and smart sensors that allow for the precise and real-time monitoring of oxidative stress and physiological responses, thus facilitating the customization of training and nutritional regimes. Observations from this review emphasize significant variability among individuals in responses to oxidative stress, highlighting the need for a personalized approach in formulating intervention strategies. It is crucial to develop and implement well-monitored, personalized supplementation protocols to ensure that each member of the military personnel receives a regimen tailored to their specific needs, thereby maximizing the effectiveness of measures to combat oxidative stress. This analysis makes a valuable contribution to the specialized literature, proposing a detailed framework for addressing oxidative stress in the armed forces and opening new directions for future research with the aim of optimizing clinical practices and improving the health and performance of military personnel under stress and specific challenges of the military field.

Uncommon Presentation of Gastric Duplication Cyst with Left-Sided Portal Hypertension: A Case Report and Literature Review.

Gastric duplication cysts (GDCs) in adults are exceedingly rare, with only a few documented cases in medical literature. The spectrum of clinical presentations varies widely, ranging from asymptomatic to severe symptoms such as hematemesis, vomiting or abdominal pain. Among the less common complications associated with GDCs, segmental portal hypertension is a notable rarity. We present a compelling case report of a patient exhibiting signs of segmental portal hypertension, where ultrasound and echo-endoscopy revealed a sizable gastric duplication cyst as the underlying etiology. Recognizing the scarcity of literature on GDCs in adult patients, we conducted a thorough review to underscore the diagnostic significance of ultrasonography and endoscopic ultrasound (EUS) in accurately identifying these congenital anomalies. This case report and comprehensive literature review emphasize the pivotal role of EUS and abdominal ultrasound in achieving an accurate diagnosis of GDCs. By shedding light on the diagnostic and therapeutic intricacies, we aim to raise awareness among clinicians regarding this rare pathology and the importance of multimodal imaging approaches for optimal patient management.

Unveiling the Pathological Mechanisms of Death Induced by SARS-CoV-2 Viral Pneumonia.

In this comprehensive study of 15 deceased patients with confirmed SARS-CoV-2 infection, spanning a time frame of 1 to 68 days from confirmation to death, autopsies were meticulously conducted with stringent safety measures. Clinical, laboratory, histopathological, and molecular analyses were integrated, shedding light on diverse pulmonary lesions, including acute inflammatory changes, vascular abnormalities, and aberrant regenerative processes. Immunohistochemical analysis, utilizing various markers, successfully identified the SARS-CoV-2 nucleocapsid antigen within infected tissue cells and also revealed what type of inflammatory cells are involved in COVID-19 pathogenesis. Molecular investigations through rt-qPCR revealed the persistent presence and varying quantities of viral genes, even after 68 days. Moreover, the viral nucleocapsid was present even in patients who died after 50 days of infection onset. Employing statistical analyses such as Chi-square and phi coefficient tests, significant associations among microscopic lesions and their correlation with molecular and immunohistochemical findings were elucidated. We could draw a map of what kind of lesions were a direct consequence of viral invasion and what lesions where secondary to the acute immunological response. This integrative approach enhances our understanding of the intricate relationships between pathological features, providing valuable insights into the multifaceted landscape of COVID-19 pathogenesis.

Antimicrobial Treatment Challenges in the Management of Infective Spondylodiscitis Associated with Hemodialysis: A Comprehensive Review of Literature and Case Series Analysis.

Infective spondylodiscitis (ISD), the infection of vertebral bodies and surrounding tissues, is a rare complication with major impact on the long-term survival of hemodialysis (HD) patients. Although the most frequent etiology is staphylococcal, identifying these pathogens in blood cultures and biopsy cultures is often difficult. This paper aims to present suitable antibiotic combinations for the treatment of these patients, which is usually challenging in the case of an unidentified pathogen. We presented the therapies applied for 13 HD patients and 19 patients without chronic kidney disease (CKD), diagnosed with ISD between 2013 and 2023 in Bihor County. The percentage of positive blood cultures was low in both groups (30.78% HD vs. 15.78% non-HD). The average length of antibiotic therapy was 5.15 weeks in HD patients and 6.29 weeks in non-HD patients. The use of Carbapenem alone (e.g., Meropenem) for an average of 19.6 days for patients in HD when the pathogen was not identified has proven to be efficient in most cases, similarly to using Vancomycin and Fluoroquinolone/Cephalosporines in combination. Regarding the non-CKD patients, the use of Clindamycin in various combinations for an average of 30.3 days has proven to be efficient in more than 90% of cases of ISD with a nonidentified pathogen. Within 2 years after ISD was diagnosed, 12 of the 13 HD patients passed away, mainly due to cardiovascular causes. Unfortunately, there are no guidelines in the literature concerning the empiric treatment of ISD in the particular case of HD patients. Upon checking the literature on PubMed and Google Scholar, only 10 studies provided relevant data regarding ISD treatment for HD patients. More data about the treatment and evolution of these patients is needed in order to elaborate a truly relevant metanalysis.

Medical and Cardiac Risk Stratification and Exercise Prescription in Persons With Cancer.

ABSTRACT: Cancer patients are recommended to exercise at all stages of disease given the multiple health and functional benefits of physical activity. Certain safety precautions, including a preparticipation medical evaluation and periodic re-evaluations, should be undertaken before creating an exercise program based on individual cancer and treatment history. When designing an exercise program, physiatrists should use similar principles of frequency, intensity, timing, and type for cancer patients that are used for noncancer patients. Special attention to risks of cardiac and pulmonary disease along with risks of sarcopenia, thrombocytopenia, anemia, neutropenia, fracture risk, neurotoxicity, lymphedema, and metastases should be made. This article will outline these specific risks and necessary modifications to the exercise prescription for cancer patients that can be used to enable safe participation in recommended exercise.

Development of a Cancer Rehabilitation Dashboard to Collect Data on Physical Function in Cancer Patients and Survivors.

OBJECTIVE: The aim of the study is to describe the development of a cancer rehabilitation dashboard that collects data on physical function for cancer survivors in a cancer institute. METHODS: This project was conducted at the Miami Cancer Institute. The cancer rehabilitation dashboard was developed by a team of physicians, biostatistician, and medical informatics teams to record, report and track the physical function of cancer survivors. A multimodal approach to the measurement of physical function was used and included the Patient-Reported Outcome Measurement Information System-Physical Function short form, Patient-Reported Outcome Measurement Information System-Fatigue short form, Timed Up and Go Test, Sit-to-Stand Test in 30-sec test, four-stage balance test, and grip strength. To develop this system, a Cerner Power Form was developed based on the physical function data. To display the data, a dedicated flowsheet was developed and placed within the Oncology Viewpoint in Cerner Millennium. Thus, from inside any patient record, the flowsheet could easily be accessed by providers without leaving normal clinician workflows. Using native functionality, the data can also be shown in graphical format to facilitate dialog with patients and oncology teams. All patient data from the Cerner Power Form discrete task assays were integrated into an existing Oncology Data Warehouse for all patients. The data elements in the Cerner Power Form were identified in the electronic medical record system, loaded into the Oncology Data Warehouse, and related to the other source systems to develop reports and data visualizations such as the cancer rehabilitation dashboard. The cancer rehabilitation dashboard allows visualization of numerous parameters of physical function in cancer survivors evaluated and treated and their change over time. Rendered in Tableau, the cancer rehabilitation dashboard acts as a centralized, interactive data source to analyze and connect clinicians to near real-time data. RESULTS: The cancer rehabilitation dashboard was successfully developed and implemented into a cancer rehabilitation practice in a cancer institute and used to collect and track physical function data for cancer survivors receiving treatment and cancer survivors. This information has been used to direct the treatment plan and educate individual patients about the impact of the cancer and its treatment on physical function as well as oncology teams in a cancer institute. CONCLUSIONS: The cancer rehabilitation dashboard provides an insight into the physical function of cancer survivors receiving treatment and cancer survivors using both self-reported and objective metrics. It can be customized to suit the interests of clinicians and researchers wishing to improve the quality of life of this population.

Predictors of Post-ERCP Pancreatitis (P.E.P.) in Choledochal Lithiasis Extraction.

In the present era, post-ERCP pancreatitis (PEP) stands out as one of the most commonly occurring complications associated with endoscopic choledochal lithiasis extraction. The ability to predict the occurrence of such an event, particularly by utilizing absolute values and ratio dynamics of the emergency blood tests, constitutes the primary step in effectively managing a patient with a complex pathology. The study involved 134 patients who performed ERCP to extract choledochal lithiasis (n = 48 with PEP and n = 86 without PEP). The results revealed increased risks of post-ERCP pancreatitis in women and lower risks in those who benefited from manipulation of the main bile duct with the Dormia probe and dilatation balloon (OR: 2.893 CI 95%: 1.371-6.105, p = 0.005 and respectively OR: 0.346 CI 95%: 0.156-0.765, p = 0.009), without biliary stent placement. Moreover, the results brought novel elements to the literature, showing that higher values of CRPR (OR: 4.337 CI 95%: 1.945-9.668; p < 0.001), TBIR (4.004 CI 95%: 1.664-9.634; p = 0.002) and NLR post-ERCP (3.281 CI 95%: 1.490-7.221; p = 0.003) are predictive for PEP. Nevertheless, lower total bilirubin levels upon admission are predictive of PEP with an OR of 5.262 (95% confidence interval: 2.111-13.113, p < 0.001).

Primary percutaneous closure of a traumatic ventricular septal defect after stab wound to the chest: a case report.

Background: Traumatic ventricular septal defects (VSDs) are life-threatening complications of blunt or stab chest trauma. The standard of care is surgical closure or secondary percutaneous closure due to high surgical risk because of recent sternotomy. Case summary: We present a 22-year-old male with an ice pick-related VSD. It was successfully closed by primary percutaneous approach. After 6 months, the echo Doppler shows no residual shunt, normal pulmonary artery pressure, and normal biventricular function. Discussion: To our knowledge, this is one of the first primary percutaneous closures for knife-related VSD. Early diagnosis and treatment can prevent heart failure and long-term complications. Less necrotic tissue surrounding the VSD compared with post-infarction (PI) VSD allows for early and secure treatment. Percutaneous closure is a feasible and effective choice even in patients who had no prior sternotomy or who reject surgery as a primary treatment strategy.

Characterization of Physical Function and Cancer-Related Physical Impairments in Hispanic Women With Breast Cancer: A Descriptive Study.

Introduction: This study reports characteristics of Hispanic women with breast cancer with respect to physical function, body mass index (BMI), and depression. Methods: This retrospective study included 322 Hispanic women with breast cancer. Physical function and fatigue were assessed using the Patient Reported Outcomes Measurement System-Physical Function (PROMIS-PF) short form and PROMIS-Fatigue (PROMISE-F) short form. In addition, Timed Up and Go (TUG) test, sit to stand in 30 s (STS30) test, four-stage balance test (4SB), and grip strength (GS) were measured. Depression was identified using Patient Health Questionnaire (PHQ)-2 and extracted from medical chart. Results: Nearly 40.8% were obese, and 20.8% had depression. Compared to normal BMI patients, mean PROMIS-F score was significantly higher among overweight and obese patients. The mean STS30 score was significantly lower in obese patients, compared to normal BMI patients. Regression analysis showed that the odds of depression were higher with increasing TUG and lower PROMIS-F, STS30, and GS. Conclusion: Hispanic women with breast cancer have substantial loss of physical function, and this is exaggerated if they are obese, overweight, or depressed. Clinicians caring for this population should screen them for the presence of loss of physical function, BMI, and depression.

Therapeutic Perspectives for Microbiota Transplantation in Digestive Diseases and Neoplasia-A Literature Review.

In a mutually beneficial connection with its host, the gut microbiota affects the host's nutrition, immunity, and metabolism. An increasing number of studies have shown links between certain types of disease and gut dysbiosis or specific microorganisms. Fecal microbiota transplantation (FMT) is strongly advised for the treatment of recurrent or resistant Clostridium difficile infection (CDI) due to its outstanding clinical effectiveness against CDI. The therapeutic potential of FMT for other disorders, particularly inflammatory bowel diseases and malignancies, is currently gaining more and more attention. We summarized the most recent preclinical and clinical evidence to show the promise of FMT in the management of cancer as well as complications related to cancer treatment after reviewing the most recent research on the gut microbiota and its relationship to cancer.

Effect of Frailty on Hospital Outcomes Among Pediatric Cancer Patients in the United States: Results From the National Inpatient Sample.

BACKGROUND: Studies on frailty among pediatric patients with cancer are scarce. In this study, we sought to understand the effects of frailty on hospital outcomes in pediatric patients with cancer. METHODS: This retrospective study used data collected and stored in the Nationwide Inpatient Sample (NIS) between 2005 and 2014. These were hospitalized patients and hence represented the sickest group of patients. Frailty was measured using the frailty definition diagnostic indicator by Johns Hopkins Adjusted Clinical Groups. RESULTS: Of 187,835 pediatric cancer hospitalizations included in this analysis, 11,497 (6.1%) were frail. The average hospitalization costs were $86,910 among frail and $40,358 for nonfrail patients. In propensity score matching analysis, the odds of in-hospital mortality (odds ratio, 2.08; 95% CI, 1.71-2.52) and length of stay (odds ratio, 3.76; 95% CI, 3.46-4.09) were significantly greater for frail patients. The findings of our study suggest that frailty is a crucial clinical factor to be considered when treating pediatric cancer patients in a hospital setting. CONCLUSIONS: These findings highlight the need for further research on frailty-based risk stratification and individualized interventions that could improve outcomes in frail pediatric cancer patients. The adaptation and validation of a frailty-defining diagnostic tool in the pediatric population is a high priority in the field.

Failure in Medical Practice: Human Error, System Failure, or Case Severity?

The success rate in medical practice will probably never reach 100%. Success rates depend on many factors. Defining the success rate is both a technical and a philosophical issue. In opposition to the concept of success, medical failure should also be discussed. Its causality is multifactorial and extremely complex. Its actual rate and its real impact are unknown. In medical practice, failure depends not only on the human factor but also on the medical system and has at its center a very important variable-the patient. To combat errors, capturing, tracking, and analyzing them at an institutional level are important. Barriers such as the fear of consequences or a specific work climate or culture can affect this process. Although important data regarding medical errors and their consequences can be extracted by analyzing patient outcomes or using quality indicators, patient stories (clinical cases) seem to have the greatest impact on our subconscious as medical doctors and nurses and these may generate the corresponding and necessary reactions. Every clinical case has its own story. In this study, three different cases are presented to illustrate how human error, the limits of the system, and the particularities of the patient's condition (severity of the disease), alone or in combination, may lead to tragic outcomes There is a need to talk openly and in a balanced way about failure, regardless of its cause, to look at things as they are, without hiding the inconvenient truth. The common goal is not to find culprits but to find solutions and create a culture of safety.

Effect of frailty on hospital outcomes among patients with cancer in the United States: Results from the National Inpatient Sample.

INTRODUCTION: To understand the effects of frailty on hospital outcomes such as in-hospital mortality, length of stay, and healthcare cost among patients with cancer using a nationally representative database. MATERIALS AND METHODS: This study was a retrospective observational analysis of Nationwide Inpatient Sample (NIS) data collected during 2005-2014. Participants included adult patients with cancer ≥45 years identified by International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. 'Frail' versus 'non-frail' hospitalizations were determined using the Johns Hopkins Adjusted Clinical Groups (ACG) frailty-defining diagnosis indicator. Main outcome measures were in-hospital mortality, hospital length of stay, and hospitalization cost. We defined prolonged length of stay as hospital stay ≥75th percentile of the study sample. Propensity score match analysis was done to examine whether frailty was associated with length of stay and in-hospital mortality. RESULTS: There were 10,463,083 cancer hospitalizations during 2005-2014, of which 1,022,777 (9.8%) were frail. Patients having length of stay ≥8 days were significantly higher among frail group, compared to non-frail group (53.3% versus 25.3%, P < 0.001). Similarly, unadjusted mortality (12.0% versus 5.3%, P < 0.001) and hospitalization costs ($29,726 versus $18,595, P < 0.001) were significantly higher for frail patients. Nearly $28 billion was expended on hospitalization of frail patients with cancer during the study period. In propensity score match analysis, the odds of in-hospital mortality (odds ratio [OR], 1.54; 95% confidence interval [CI], 1.50-1.58) and length of stay (OR, 2.23; 95% CI, 2.18-2.27) were significantly greater for frail patients. DISCUSSION: Frailty was associated with adverse hospital outcomes such as increased length of stay, mortality, and hospitalization cost among all cancer types. Our findings could be valuable for frailty-based risk stratification of patients with cancer. Concerted efforts by the physiatrists, oncologists, and surgeons towards identifying frailty and incorporating it in risk estimation measures could help in optimizing management strategies for cancer.

Impact of Frailty on Hospital Outcomes Among Patients with Lymphoid Malignancies Receiving Autologous Hematopoietic Stem Cell Transplantation in the United States.

BACKGROUND: Frailty could affect outcomes of autologous hematopoietic stem cell transplantation (aHSCT). This study sought to examine the effects of frailty on hospital outcomes among patients with non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), and multiple myeloma (MM) who received aHSCT. MATERIALS AND METHODS: This study was a retrospective analysis of Nationwide Inpatient Sample database, 2005 to 2014. Outcome variables were in-hospital mortality, prolonged length of stay and hospitalization cost. Frail patients were defined using the Johns Hopkins Adjusted Clinical Groups frailty-defining diagnosis indicator. RESULTS: There were 20,573 NHL, 8,974 HL, and 40,750 MM patients. Among them, 5.5% NHL, 3.8% HL, and 4.8% MM patients were frail. Among patients with NHL, there were significant associations between frailty and in-hospital mortality (Odds Ratio [OR], 4.04, 95% CI: 2.11-7.76), and prolonged length of stay (OR, 2.32, 95% CI: 1.56-3.46). Similarly, among HL, there were significant associations between frailty and in-hospital mortality (OR, 1.82, 95% CI: 1.43-2.76), and prolonged length of stay (OR, 1.55, 95% CI: 1.34-2.84). Likewise, for MM, there were significant associations between frailty and in-hospital mortality (OR, 4.28, 95% CI: 2.16-8.48), and prolonged length of stay (OR, 3.00, 95% CI: 2.00-4.51). These associations remained significant after stratifying by age and comorbidities. Significant differences were observed in hospitalization cost between frail and non-frail patients. CONCLUSION: Among patients with lymphoid malignancies undergoing HSCT, frailty was associated with greater in-hospital mortality, longer length of stay, and higher hospitalization costs. Comprehensive health status assessments for identifying and managing frail patients in this population could improve patient outcomes.

Music Upper Limb Therapy-Integrated Provides a Feasible Enriched Environment and Reduces Post-stroke Depression: A Pilot Randomized Controlled Trial.

OBJECTIVE: This study's aims were to refine Music Upper Limb Therapy-Integrated (MULT-I) to create a feasible enriched environment for stroke rehabilitation and compare its biologic and behavioral effects with that of a home exercise program (HEP). DESIGN: This was a randomized mixed-methods study of 30 adults with post-stroke hemiparesis. Serum brain-derived neurotrophic factor and oxytocin levels measured biologic effects, and upper limb function, disability, quality of life, and emotional well-being were assessed as behavioral outcomes. Participant experiences were explored using semistructured interviews. RESULTS: MULT-I participants showed reduced depression from preintervention to postintervention as compared with HEP participants. Brain-derived neurotrophic factor levels significantly increased for MULT-I participants but decreased for HEP participants, with a significant difference between groups after excluding those with post-stroke depression. MULT-I participants additionally improved quality of life and self-perceived physical strength, mobility, activity, participation, and recovery from preintervention to postintervention. HEP participants improved upper limb function. Qualitatively, MULT-I provided psychosocial support and enjoyment, whereas HEP supported self-management of rehabilitation. CONCLUSIONS: Implementation of a music-enriched environment is feasible, reduces post-stroke depression, and may enhance the neural environment for recovery via increases in brain-derived neurotrophic factor levels. Self-management of rehabilitation through an HEP may further improve upper limb function.

Avocado Oil Prevents Kidney Injury and Normalizes Renal Vasodilation after Adrenergic Stimulation in Hypertensive Rats: Probable Role of Improvement in Mitochondrial Dysfunction and Oxidative Stress.

Hypertension impairs the function of the kidney and its vasculature. Adrenergic activation is involved in these processes by promoting oxidative stress and mitochondrial dysfunction. Thus, the targeting of mitochondrial function and mitochondrial oxidative stress may be an approach to alleviate hypertensive kidney damage. Avocado oil, a source of oleic acid and antioxidants, improves mitochondrial dysfunction, decreases mitochondrial oxidative stress, and enhances vascular function in hypertensive rats. However, whether avocado oil improves the function of renal vasculature during the adrenergic stimulation, and if this is related to improvement in renal damage and enhancement of mitochondrial activity is unknown. Thus, the effects of avocado oil on renal vascular responses to adrenergic stimulation, mitochondrial dysfunction, oxidative stress, and renal damage were compared with prazosin, an antagonist of α1-adrenoceptors, in hypertensive rats induced by L-NAME. Avocado oil or prazosin decreased blood pressure, improved endothelium-dependent renal vasodilation, prevented mitochondrial dysfunction and kidney damage in hypertensive rats. However, avocado oil, but not prazosin, decreased mitochondrial ROS generation and improved the redox state of mitochondrial glutathione. These results suggest that avocado oil and prazosin prevented hypertensive renal damage due to the improvement in mitochondrial function.

The Interference between SARS-CoV-2 and Tyrosine Kinase Receptor Signaling in Cancer.

Cancer and viruses have a long history that has evolved over many decades. Much information about the interplay between viruses and cell proliferation and metabolism has come from the history of clinical cases of patients infected with virus-induced cancer. In addition, information from viruses used to treat some types of cancer is valuable. Now, since the global coronavirus pandemic erupted almost a year ago, the scientific community has invested countless time and resources to slow down the infection rate and diminish the number of casualties produced by this highly infectious pathogen. A large percentage of cancer cases diagnosed are strongly related to dysregulations of the tyrosine kinase receptor (TKR) family and its downstream signaling pathways. As such, many therapeutic agents have been developed to strategically target these structures in order to hinder certain mechanisms pertaining to the phenotypic characteristics of cancer cells such as division, invasion or metastatic potential. Interestingly, several authors have pointed out that a correlation between coronaviruses such as the SARS-CoV-1 and -2 or MERS viruses and dysregulations of signaling pathways activated by TKRs can be established. This information may help to accelerate the repurposing of clinically developed anti-TKR cancer drugs in COVID-19 management. Because the need for treatment is critical, drug repurposing may be an advantageous choice in the search for new and efficient therapeutic compounds. This approach would be advantageous from a financial point of view as well, given that the resources used for research and development would no longer be required and can be potentially redirected towards other key projects. This review aims to provide an overview of how SARS-CoV-2 interacts with different TKRs and their respective downstream signaling pathway and how several therapeutic agents targeted against these receptors can interfere with the viral infection. Additionally, this review aims to identify if SARS-CoV-2 can be repurposed to be a potential viral vector against different cancer types.

The pioneer use of a modified PRGF-Endoret® technique for wound healing in a hemodialyzed diabetic patient in a terminal stage of renal disease.

In the literature, this paper is the first to describe the use of plasma rich in growth factors (PRGF)-Endoret® in hemodialyzed diabetic patients, to promote the healing of after amputation wounds. The PRGF-Endoret® was primarily conceived to be used in maxillofacial surgery, oral implantology, etc., the innovation residing in the blood collection technique (quantity, moment of the week, rhythmicity), which was adapted to the specific conditions of the hemodialyzed patient. Moreover, in the initial phases, the two PRGF fractions were innovatively applied as single alternating layers on the wound surface. Only after the surface of the wound decreased, the two PRGF fractions were applied as overlapping layers. Nevertheless, the paper presents the optimal method to assess the clinical evolution of the wound. Histopathological examination of the biopsy performed during wound preparation for PRGF application brought additional, essential data for orienting the therapeutic approach. The exclusion of calciphylaxis, a disease with high mortality risk, encouraged the application of this method, and also demonstrated the microscopic features in hemodialyzed diabetic patients.

[D-Leu1]MC-LR Has Lower PP1 Inhibitory Capability and Greater Toxic Potency than MC-LR in Animal and Plant Tissues.

Two microcystins, MC-LR and [D-Leu1]MC-LR, present in La Plata Basin blooms, are differentiated by substitution of D-Alanine for D-Leucine at position 1. Our objective was to evaluate acute toxicity of [D-Leu1]MC-LR and MC-LR in mice (N:NIH Swiss) and beans (Phaseolus vulgaris). We observed variations in [D-Leu1]MC-LR lethal doses with respect to those reported for MC-LR (100 µg/kg), with an increased liver/body weight ratio and intrahepatic hemorrhages in mice exposed to 50-200 µg [D-Leu1]MC-LR/kg and slight steatosis after a single 25 µg [D-Leu1]MC-LR/kg i.p. dose. Our study in the plant model showed alterations in germination, development, morphology and TBARs levels after a single contact with the toxins during imbibition (3.5 and 15 µg/mL), those treated with [D-Leu1]MC-LR being more affected than those treated with the same concentration of MC-LR. Protein phosphatase 1 (PP1) IC50 values were 40.6 nM and 5.3 nM for [D-Leu1]MC-LR and MC-LR, respectively. However, the total phosphatase activity test in root homogenate showed 60% inhibition for [D-Leu1]MC-LR and 12% for MC-LR. In mouse liver homogenate, 50% inhibition was observed for [D-Leu1]MC-LR and 40% for MC-LR. Our findings indicate the need for further research into [D-Leu1]MC-LR toxicity since together with oxidative stress, the possible inhibition of other phosphatases could explain the differences detected in the potency of the two toxins.