Comparative analysis of the effectiveness of inhibitor-protected cephalosporins fortified with basic antibiotic

Inhibitor-protected cephalosporins are an important tool against hospital infections caused by extended spectrum β-lactamase producers. At the same time, the relative deficiency of the basic antibiotic in combination with the β-lactamase inhibitor sulbactam (1: 1) may be associated with the risk of therapeutic failure.Objective. To compare therapeutic effect of various regimens for prescribing inhibitor-protected cephalosporins in children with severe bacterial infection.Children characteristics and research methods. The authors compared clinical efficacy of cefotaxime / sulbactam, cefoperazone / sulbactam, cefepime / sulbactam at maximum doses and main component-fortified-cefepime / sulbactam. The study included 92 patients aged from 2 months to 12 years with appendicular peritonitis, acute purulent osteomyelitis, complicated hospital infections of the lower respiratory tract, exacerbation of chronic purulent otitis media and chronic urinary tract infections. It was found that inhibitor-protected cephalosporins with a 1: 1 ratio of components more often necessitated a change in therapy. The use of drugs initially containing a basic antibiotic in a high dose (component ratio 2:1) or additionally fortified with a basic antibiotic demonstrated a higher therapeutic efficacy.

Evaluation of recombinant human erythropoietin responsiveness by measuring erythrocyte creatine content in haemodialysis patients

Background One of the main causes of anaemia in patients with end-stage renal disease is relative deficiency in erythropoietin production. Eythropoiesis stimulating agent (ESA), a potent haematopoietic growth factor, is used to treat anaemia in haemodialysis patients. The effect of ESA is usually assessed by haematological indices such as red blood cell count, haemoglobin concentration and haematocrit, but erythrocyte indices do not provide information of the rapid change in erythropoietic activity. As erythrocyte creatine directly assess erythropoiesis, the aim of this study was to evaluate the effect of ESA in haemodialysis patients by measuring the erythrocyte creatine content. Methods ESA dose was fixed 3 months prior to the enrollment and was maintained throughout the entire study period. Erythrocyte creatine was measured with haematologic indices in 83 haemodialysis patients. Haemoglobin was also measured 3 months after. Results ESA dose (152.4 ± 62.9 vs. 82.2 ± 45.5 units/kg/week, P = 0.0001) and erythrocyte creatine (2.07 ± 0.73 vs. 1.60 ± 0.41 μmol/gHb, p = 0.0003) were significantly higher in 27 patients with haemoglobin <10 g/dL compared to 56 patients with haemoglobin ≥10 g/dL. There was a fair correlation between ESA dose and the concentration of creatine in the erythrocytes (r = 0.55, P < 0.0001). Increase in haemoglobin (>0.1 g/dL) was observed in 37 patients, whereas haemoglobin did not increase in 46 patients. Erythrocyte creatine levels were significantly higher in those patients with an increase in haemoglobin compared to those without (2.04 ± 0.64 vs. 1.52 ± 0.39 μmol/gHb, p < 0.0001). When 8 variables (ESA dose, erythropoietin resistance index, C-reactive protein, intact parathyroid hormone, iron supplementation, presence of anaemia, erythrocyte creatine and reticulocyte) were used in the multivariate logistic analysis, erythrocyte creatine levels emerged as the most important variable associated with increase in haemoglobin (Chi-square = 6.19, P = 0.01). Conclusion Erythrocyte creatine, a useful marker of erythropoietic capacity, is a reliable marker to estimate ameliorative effectiveness of ESA in haemodialysis patients.

Addressing the ‘hypoxia paradox’ in severe COVID-19: literature review and report of four cases treated with erythropoietin analogues

Background Since fall 2019, SARS-CoV-2 spread world-wide, causing a major pandemic with estimated ~ 220 million subjects affected as of September 2021. Severe COVID-19 is associated with multiple organ failure, particularly of lung and kidney, but also grave neuropsychiatric manifestations. Overall mortality reaches > 2%. Vaccine development has thrived in thus far unreached dimensions and will be one prerequisite to terminate the pandemic. Despite intensive research, however, few treatment options for modifying COVID-19 course/outcome have emerged since the pandemic outbreak. Additionally, the substantial threat of serious downstream sequelae, called ‘long COVID’ and ‘neuroCOVID’, becomes increasingly evident. Main body of the abstract Among candidates that were suggested but did not yet receive appropriate funding for clinical trials is recombinant human erythropoietin. Based on accumulating experimental and clinical evidence, erythropoietin is expected to (1) improve respiration/organ function, (2) counteract overshooting inflammation, (3) act sustainably neuroprotective/neuroregenerative. Recent counterintuitive findings of decreased serum erythropoietin levels in severe COVID-19 not only support a relative deficiency of erythropoietin in this condition, which can be therapeutically addressed, but also made us coin the term ‘hypoxia paradox’. As we review here, this paradox is likely due to uncoupling of physiological hypoxia signaling circuits, mediated by detrimental gene products of SARS-CoV-2 or unfavorable host responses, including microRNAs or dysfunctional mitochondria. Substitution of erythropoietin might overcome this ‘hypoxia paradox’ caused by deranged signaling and improve survival/functional status of COVID-19 patients and their long-term outcome. As supporting hints, embedded in this review, we present 4 male patients with severe COVID-19 and unfavorable prognosis, including predicted high lethality, who all profoundly improved upon treatment which included erythropoietin analogues. Short conclusion Substitution of EPO may—among other beneficial EPO effects in severe COVID-19—circumvent downstream consequences of the ‘hypoxia paradox’. A double-blind, placebo-controlled, randomized clinical trial for proof-of-concept is warranted.

Pathophysiology of COVID-19: Everywhere You Look You Will See ACE2!

Angiotensin converting enzyme 2 (ACE2) seems to be a central actor in the pathophysiology of SARS-Cov-2 infection. First, it acts as the receptor for the virus and permits its attachment to cells expressing ACE2. Second, the relative deficiency of ACE2 during infection could be linked to several clinical features encountered during the disease, like ARDS and coagulation abnormalities. This study explores the strong link between ACE2 and the majority of risk factors for the severe evolution of COVID-19. It seems that all these risks factors are linked to an increased level of ACE2 and/or imbalance in ACE/ACE2.

Science

There was a strong desire within psychopharmacology to find a firm scientific basis for the field, hoping to ensure that it was regarded as a science. This chapter explains how the pseudo-scientific proposition on drug efficacy has become the notion that patients are suffering from “chemical imbalances.” It also emphasizes the industry’s leaping on chemical imbalance from the very beginning, because it sounded so plausible and so scientific that patients could easily grasp it. The chapter refers to a 1976 ad for USV’s tricyclic antidepressant Pertofrane that promised higher norepinephrine levels through reuptake blockade. It explains how depressions are associated with an absolute or relative deficiency of catecholamines, particularly norepinephrine.

A CLINICAL STUDY TO EVALUATE THE ANTIHYPERGLYCEMIC ACTIVITY OF BHANDIRA

Introduction: Madhumeha (Diabetes mellitus) is a life style related, multifactorial disease with multiple facets involving all the Srotas, Dhatus and the Ojas. Madhumeha is a Vataja variety of Prameha, which manifests either due to Margavarana or due to Dhatu Kshaya. Diabetes mellitus is a clinical syndrome characterized by Hyperglycemia due to absolute or relative deficiency of insulin. Diabetes and its complication pose a major threat to future public health resources throughout the world. In this study an effort has been made to evaluate the Madhumehahara karma (Antihyperglycemic activity) of Bhandira (Clerodendrum infortunatum auct Non Linn) Materials and methods: The present study was an open labelled, single arm, clinical study in Madhumeha (Diabetes mellitus) (n=30) selected using convenience sampling technique with pre and post design conducted in a tertiary Ayurveda healthcare centre attached to a teaching institute, situated at the district headquarters in South India. 32 patients fulfilling the inclusion criteria suffering from Madhumeha w s r to Diabetes mellitus were selected with the intervention of Bhandira patra vati 3 Twice in a day (BD) for 30 days. Results: The effect of therapy was assessed before and after treatment, the results were statistically analyzed; it showed significant changes in subjective parameters like praboota mutrata, avila mootrata, kshudadikya, karapada daha, and Objective parameter- Fasting Blood Sugar (FBS), Post Prandial Blood Sugar (PPBS), Fasting Urine Sugar (FUS), Post Prandial Urine Sugar (PPUS) Conclusion: Bhandira patra vati in a dose of 3 BD before food has shown better efficacy in subjective parameters like praboota mutrata, avila mootrata, kshudadikya, karapada daha, and Objective parameter like- FBS, PPBS, FUS, PPUS KEY WORDS: Madhumeha, Anti-hyperglycaemic, Bhandira patra vati

Evaluation of the Antidiabetic and Antihyperlipidemic Activity of Spondias purpurea Seeds in a Diabetic Zebrafish Model

Diabetes mellitus (DM) is a serious chronic degenerative disease characterized by high levels of glucose in the blood. It is associated with an absolute or relative deficiency in the production and/or action of insulin. Some of the complications associated with DM are heart disease, retinopathy, kidney disease, and neuropathy; therefore, new natural alternatives are being sought to control the disease. In this work, we evaluate the antidiabetic effect of Spondias purpurea seed methanol extract (CSM) in vitro and in a glucose-induced diabetic zebrafish model. CSM is capable of lowering blood glucose and cholesterol levels, as well as forming advanced glycation end-products, while not presenting toxic effects at the concentrations evaluated. These data show that CSM has a promising antidiabetic effect and may be useful in reducing some of the pathologies associated with diabetes mellitus.

Prevalence of Various Sign and Symptoms of Diabetic Peripheral Neuropathy

BACKGROUND: Diabetes mellitus (DM) is a chronic metabolic syndrome marked by hyperglycemia due to absolute or relative deficiency of insulin hormone. Diabetic neuropathy is a complication of both type 1 and type 2 diabetes. Although pain is one of the most dominant symptoms of diabetic neuropathy, its pathophysiological mechanisms yet unknown. Toxic effects of high glucose levels play an important role in the development of this complication. METHODOLOGY: Data was collected through the questionnaire regarding Clinical findings, medical records, weight, age, family history, different habits, and psychogenic behavior. All the patients with the mentioned diseases are included in this study, excluding the mentally ill patients and the pregnant women. RESULT: The result of the present study showed that diabetic neuropathy is the most common complication of diabetes mellitus. It has been observed that most of the patients due to lack of awareness are suspected to the elevated or extreme blood sugar level which leads to neuropathy. Due to the Diabetic Peripheral Neuropathy (DPN) most of the patients suffering from foot problems, foot ulcers and then amputations. Lack of awareness, lack of health management, obesity, blood pressure changes, less care plays a key role in increasing the chances of diabetic neuropathy. COCLUSION: Diabetic neuropathy had very bad influence on a person’s health and daily activities. The Patient education programs need to emphasize on large scale. The ultimate aim of this study is the foot care education for people with the diabetes and to prevent foot ulcers and amputation.

Social Value and Urban Sustainability in Food Markets

Urban food markets can promote sustainable development through the generation of social value in the spaces where they are located and contribute to sustainability on a global scale. To measure this, indicators are required to evaluate and monitor these markets. Studies in this regard are scarce and often developed according to top-down schemes. This study seeks to remedy this relative deficiency and aims to design specific social sustainability metrics for these organizations from a bottom-up perspective. The Integrated Social Value model is used. This social accounting system is considered appropriate in this study due to the phenomenological approach on which it is based and is applied to a service cooperative located in the Canary Islands. The main contribution of this work is that new social sustainability indicators are obtained and applied to the analysis of an entity, and they are relevant and understandable to stakeholders. This would provide, in future developments, a system of sustainability indicators for similar organizations in Spain.

Mitochondrial and Metabolic dysfunction in Friedreich ataxia: Update on Pathophysiological relevance and clinical interventions

Friedreich ataxia is a recessive disorder resulting from relative deficiency of the mitochondrial protein frataxin. Frataxin functions in the process of iron sulfur cluster synthesis. In this review, we update some of the processes downstream of frataxin deficiency that may mediate the pathophysiology. Based on cellular models, in vivo models and observations of patients, ferroptosis may play a major role in the pathogenesis of FRDA along with depletion of antioxidant reserves and abnormalities of mitochondrial biogenesis. Ongoing clinical trials with ferroptosis inhibitors and Nrf2 activators are now targeting each of the processes. In addition, better understanding of the mitochondrial events in FRDA may allow the development of improved imaging methodology for assessing the disorder. Though not technologically feasible at present, metabolic imaging approaches may provide a direct methodology to understand the mitochondrial changes occurring in FRDA and provide a methodology to monitor upcoming trials of frataxin restoration.