PANTOTHENIC ACID: AN OVERVIEW FOCUSED ON MEDICAL ASPECTS

Pantothenic acid (vitamin B5) is a water-soluble B-complex vitamin. It is of biologic importance because of its incorporation into coenzyme A and acyl carrier protein. Coenzyme A is an indispensable cofactor in all living organisms, where it functions in over 70 enzymatic pathways. Most bacteria, plants, and fungi synthesizes pantothenic acid; thus, the vitamin is found virtually everywhere in nature. Therefore, a naturally occurring vitamin deficiency in humans does not occur. Several clinical trials have been undertaken in humans using pantothenic acid supplementation in various medical fields. Unfortunately, firm conclusions regarding therapeutic effectiveness cannot be drawn from many of these studies. However, it has been suggested that there is a beneficial effect of pantethine on hyperlipidemia. Cysteamine treatment, a metabolite of the degradation of coenzyme A, has dramatically changed the course of the cystinosis; and clinical trials of this compound are underway in other medical fields. In the last few decades, several studies have pointed out the great interest of the inhibition of the coenzyme A metabolic pathway as an attractive target in developing new antimicrobial agents. Furthermore, recent research on coenzyme A metabolic enzymes has led to the discovery of uniquely nonmetabolic roles for both enzymes and their metabolites, thus opening an exciting field of investigation. In the present mini-review, we describe the current understanding of the pantothenic acid medical aspects and provide an overview on future potential therapeutic indications for this vitamin and its metabolic byproducts

PANTOTHENIC ACID: AN OVERVIEW FOCUSED ON MEDICAL ASPECTS

Pantothenic acid (vitamin B5) is a water-soluble B-complex vitamin. It is of biologic importance because of its incorporation into coenzyme A and acyl carrier protein. Coenzyme A is an indispensable cofactor in all living organisms, where it functions in over 70 enzymatic pathways. Most bacteria, plants, and fungi synthesizes pantothenic acid; thus, the vitamin is found virtually everywhere in nature. Therefore, a naturally occurring vitamin deficiency in humans does not occur. Several clinical trials have been undertaken in humans using pantothenic acid supplementation in various medical fields. Unfortunately, firm conclusions regarding therapeutic effectiveness cannot be drawn from many of these studies. However, it has been suggested that there is a beneficial effect of pantethine on hyperlipidemia. Cysteamine treatment, a metabolite of the degradation of coenzyme A, has dramatically changed the course of the cystinosis; and clinical trials of this compound are underway in other medical fields. In the last few decades, several studies have pointed out the great interest of the inhibition of the coenzyme A metabolic pathway as an attractive target in developing new antimicrobial agents. Furthermore, recent research on coenzyme A metabolic enzymes has led to the discovery of uniquely nonmetabolic roles for both enzymes and their metabolites, thus opening an exciting field of investigation. In the present mini-review, we describe the current understanding of the pantothenic acid medical aspects and provide an overview on future potential therapeutic indications for this vitamin and its metabolic byproducts

Diagnosis of leishmaniasis

This work was supported by EK Elmahallawy, who has a PhD scholarship (number 736) from Erasmus Mundus Scholarship Programme (ELEMENT Action 1 First call).Leishmaniasis is a clinically heterogeneous syndrome caused by intracellular protozoan parasites of the genus Leishmania. The clinical spectrum of leishmaniasis encompasses subclinical ( not apparent), localized (skin lesion), and disseminated (cutaneous, mucocutaneous, and visceral) infection. This spectrum of manifestations depends on the immune status of the host, on the parasite, and on immunoinflammatory responses. Visceral leishmaniasis causes high morbidity and mortality in the developing world. Reliable laboratory methods become mandatory for accurate diagnosis, especially in immunocompromised patients such as those infected with HIV. In this article, we review the current state of the diagnostic tools for leishmaniasis, especially the serological test.Erasmus Mundus Scholarship Programme (ELEMENT Action 1 First call) 73

Infectious etiology of diarrheas studied in a third-level hospital during a five-year period

Introduction and objective: Infectious diarrheas are highly frequent and responsible for a major consumption of resources. This study identified the main diarrhea-causing microorganisms in a health area of Granada (Spain) and determined changes in the epidemiologic pattern over a five-year period. Material and method: A retrospective study was conducted based on results obtained in the Microbiology Laboratory of Hospital Universitario Virgen de las Nieves (Granada, Spain). Results: Out of the 25,113 stool microbiological and/or parasitological studies ordered, 2,292 microorganisms were identified in 2,152 samples from 1,892 patients. There was a predominance of bacterial diarrheas (50.1 %), mainly caused by Campylobacter spp. (22.2 %), whose frequency increased significantly during the last two years, and by Salmonella spp. (16.4 %), whose frequency remained stable during the whole study period. We highlight the high frequency of Rotavirus (33.5 %), although a significant decrease was observed during the last two years. Salmonella spp. was more frequently detected during the summer and autumn, Campylobacter spp. during the spring, and Rotavirus during the winter. Viral processes were predominant (53.3 %) in pediatric patients, mainly Rotavirus in under 2-yr-olds, whereas bacterial processes predominated in older children and adults. Diarrhea began at community level in 84.2 % of patients, requiring hospitalization in 25.8 % of cases, and diarrhea was nosocomial in the remaining 15.8 %. Conclusions: During the study period, there was a significant increase in the frequency of diarrhea caused by Campylobacter spp., a significant reduction in the frequency of diarrhea due to Rotavirus, and no change in the frequency of diarrhea due to Salmonella spp., all of which showing a marked seasonal distribution

Streptococcus agalactiae clones infecting humans were selected and fixed through the extensive use of tetracycline

Streptococcus agalactiae (Group B Streptococcus, GBS) is a commensal of the digestive and genitourinary tracts of humans that emerged as the leading cause of bacterial neonatal infections in Europe and North America during the 1960s. Due to the lack of epidemiological and genomic data, the reasons for this emergence are unknown. Here we show by comparative genome analysis and phylogenetic reconstruction of 229 isolates that the rise of human GBS infections corresponds to the selection and worldwide dissemination of only a few clones. The parallel expansion of the clones is preceded by the insertion of integrative and conjugative elements conferring tetracycline resistance (TcR). Thus, we propose that the use of tetracycline from 1948 onwards led in humans to the complete replacement of a diverse GBS population by only few TcR clones particularly well adapted to their host, causing the observed emergence of GBS diseases in neonates. \ua9 2014 Macmillan Publishers Limited. All rights reserved

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Potential Relevance of Melatonin Against Some Infectious Agents: A Review and Assessment of Recent Research

Melatonin, a tryptophan-derived neurohormone found in animals, plants, and microbes, participates in various biological and physiological functions. Among other properties, numerous in vitro or in vivo studies have reported its therapeutic potential against many parasites, bacteria and viruses. In this concern, melatonin was found to be effective against many parasites such as Plasmodium, Toxoplasma gondii, and Trypansoma cruzi, via various mechanisms such as modulation of calcium level and/or host immune system. Likewise, a recent investigation has reported in vitro activity of melatonin against Leishmania infantum promastigotes which is the causative agent of fascinating visceral Leishmaniasis. This review was initially undertaken to summarize some facts about certain physiological and therapeutic effects of melatonin. It also reviews the effects and action mechanisms of melatonin in bacterial and viral infection besides biology of different parasites which may provide a promising strategy for control of many diseases of public health importance.Erasmus Mundus scholarshi

Diagnosis of leishmaniasis

Leishmaniasis is a clinically heterogeneous syndrome caused by intracellular protozoan parasites of the genus Leishmania. The clinical spectrum of leishmaniasis encompasses subclinical (not apparent), localized (skin lesion), and disseminated (cutaneous, mucocutaneous, and visceral) infection. This spectrum of manifestations depends on the immune status of the host, on the parasite, and on immunoinflammatory responses. Visceral leishmaniasis causes high morbidity and mortality in the developing world. Reliable laboratory methods become mandatory for accurate diagnosis, especially in immunocompromised patients such as those infected with HIV. In this article, we review the current state of the diagnostic tools for leishmaniasis, especially the serological test