STANDARDS OF MEDICAL CARE “INVASIVE CANDIDIASIS IN NEWBORNS”

Candida infection (candidiasis) is an important clinical problem in newborns who need treatment in modern intensive care units. Organ and/or systemic infections caused by these fungi are called invasive candidiasis (IC). Newborns are especially vulnerable to IC, and their incidence is 3-5 times higher than the corresponding rates in children or adults. Invasive fungal infections caused by Candida are the third most common late-onset infection in infants born with a birth weight <1500 g. IC in newborns is associated with approximately 20% mortality, and about half of survivors have serious long- term neurological damage. In recent years, new data have been obtained on the diagnosis, prevention and treatment of IC in newborns, which has determined a change in treatment recommendations. Accordingly, the need arose to ensure the compliance of our clinical practice with modern evidence-based approaches. Early diagnosis of candidiasis and prompt treatment with effective antifungal agents such as fluconazole, amphotericin B, and micafungin, when indicated, are critical to improving outcomes.

Assessment of Interactions of Drugs Prescribed for Pediatric Patients in Bangladesh

Drug-drug interactions (DDIs) represent an important clinical problem. During inpatient admissions, infants, children, and adolescents are typically exposed to different medications, increasing their risk of potential drug-drug interactions (pDDIs). While drug interactions are reported to be common, there are only few publications of the prevalence of such interactions among pediatric patients in Bangladesh. The present study tries to estimates the prevalence and characteristics of pDDI exposure of pediatric patients treated in children’s hospitals. This observational retrospective study was carried out on 155 patients admitted to a children’s hospital located at Dhaka during January 2019 to August 2019. The medications of the patients were analyzed for pDDIs by using Medscape drug interaction checker. The prescriptions were analyzed for demographic characteristics, medical and detailed drug history. Drug-drug interactions (DDIs) were evaluated for total numbers, types and severity of DDIs. Total 155 prescriptions with mean age 2.12±2.08 years were analyzed and a total of 25 pDDIs were recorded. The prevalence of pDDI was 17%, of which 12 (48%) were pharmacodynamic interactions, 10 (40%) were pharmacokinetic interactions and 3 (12%) of unknown mechanism. According to the severity of interaction, 4 (18%) cases were categorized as serious, 15 (55%) cases as moderate and 6 (27%) cases as minor. The occurrence of DDIs were significantly associated (r=0.912, p<0.05) with the number of drugs prescribed. The present study has identified pDDIs and also documented interactions in pediatrics patients. It has highlighted the need for screening prescriptions of pediatric patients for pDDIs and proactive monitoring of patients who have identified risk factors in order to promote detection and prevention of possible adverse drug interactions. Bangladesh Pharmaceutical Journal 24(2): 91-98, 2021

Electroacupuncture Attenuates Neuropathic Pain and Comorbid Negative Behavior: The Involvement of the Dopamine System in the Amygdala

Neuropathic pain (NeuP) is an important clinical problem accompanying negative mood symptoms. Neuroinflammation in the amygdala is critically involved in NeuP, and the dopamine (DA) system acts as an important endogenous anti-inflammatory pathway. Electroacupuncture (EA) can improve the clinical outcomes in NeuP, but the underlying mechanisms have not been fully elucidated. This study was designed to assess the effectiveness of EA on pain and pain-related depressive-like and anxiety-like behaviors and explore the role of the DA system in the effects of EA. Male Sprague-Dawley rats were subjected to the chronic constrictive injury (CCI) model to induce NeuP. EA treatment was carried out for 30 min once every other day for 3 weeks. The results showed that CCI caused mechanical hyperalgesia and depressive and anxiety-like behaviors in rats and neuroinflammation in the amygdala, such as an increased protein level of TNFα and IL-1β and activation of astrocytes. EA treatment significantly improved mechanical allodynia and the emotional dysfunction induced by CCI. The effects of EA were accompanied by markedly decreased expression of TNFα, IL-1β, and glial fibrillary acid protein (GFAP) in the amygdala. Moreover, EA treatment reversed CCI-induced down-regulation of DA concentration, tyrosine hydroxylase (TH) expression, and DRD1 and DRD2 receptors. These results suggest that EA-ameliorated NeuP may possibly be associated with the DA system to inhibit the neuroinflammation in the amygdala.

Biomarkers of Carotid Stenosis

Early recognition of rupture-prone atherosclerotic lesions in patients with high-graded carotid stenosis is an important clinical problem for preventing ischemic stroke. Various pathophysiological mechanisms are responsible for the progression and instability of plaques, such as changes in lipid composition, infiltration by immunoinflammatory cells and degradation of the extracellular matrix of the vascular wall by matrix metalloproteinases, enhanced inflammatory response and plaque neovascularization. These features are the main cause of plaque rupture and, as a consequence, neurologic symptoms. Therefore, matrix metalloproteinases and inflammatory factors can serve as possible markers for patients with severe unstable stenosis of carotid arteries. Due to the heterogeneity of atherosclerotic lesions, only one biomarker is not enough to reliably predict the development of a stroke. The use of a combination of biomarkers is better correlated with clinical data and, therefore, exceeds the analysis of individual factors. To increase the overall sensitivity and specificity and more reliable diagnosis of stroke in patients with symptomatic and asymptomatic carotid stenosis, the biomarker panel should include independent biomarkers. Further preclinical experiments and clinical trials are needed to assess the significance and precise definition of the threshold levels of such biomarkers before they can be used in clinical practice.

Correlation of Oxidative Stress and Hepatoprivial Syndrome in Dogs with Comorbidity of Babesiosis and Dirofilariasis

The comorbidity of babesiosis and dirofilariasis in dogs is an important clinical problem, despite the significant achievements of recent years in understanding the pathogenesis of this mixed invasion. It has been established that the leading pathogenetic component in the development of the cytolytic syndrome with this comorbidity in dogs is oxidative stress resulting from the mismatch of the prooxidant and antioxidant resources of the cell under the influence of Babesia canis parasitism. On the basis of morphological, biochemical and ultrasonographic studies, a direct correlation was found between oxidative stress and hepatoprivial syndrome in dogs with comorbidity of babesiosis and dirofilariasis. Hepatoprivial syndrome was accompanied by the development of hypochromic anaemia, leukocytosis, hyperproteinemia, hypoglycemia, a disorder of pigment metabolism and an increase in the catalytic activity of serum enzymes, which indicated a violation of the metabolic activity of the liver and damage to its parenchyma. The activation of lipid peroxidation processes in the hepatocytes contributed to an increase in the catalytic activity of the blood serum enzymes in sick animals, and to a decrease in the antioxidant defence of sick dogs, due to a relative decrease in the level of vitamin A in the blood. Thus, the comorbidity of babesiosis and dirofilariasis in dogs enhances the oxidative syndrome that underlies the pathogenetic mechanisms of this mixed invasion, thereby increasing the degree of involvement in the pathological process of the liver, which is manifested by hepatoprivial syndrome. Keywords: oxidative stress, hepatoprivial syndrome, dirofilariasis, babesiosis, mixtinvasion, dogs

The effects of cardiac stretch on atrial fibroblasts: analysis of the evidence and potential role in atrial fibrillation

Atrial fibrillation (AF) is an important clinical problem. Chronic pressure/volume overload of the atria promotes AF, particularly via enhanced extracellular matrix (ECM) accumulation manifested as tissue fibrosis. Loading of cardiac cells causes cell stretch that is generally considered to promote fibrosis by directly activating fibroblasts, the key cell type responsible for ECM production. The primary purpose of this article is to review the evidence regarding direct effects of stretch on cardiac fibroblasts, specifically: (i) the similarities and differences among studies in observed effects of stretch on cardiac fibroblast function; (ii) the signalling pathways implicated; and (iii) the factors that affect stretch-related phenotypes. Our review summarizes the most important findings and limitations in this area and gives an overview of clinical data and animal models related to cardiac stretch, with particular emphasis on the atria. We suggest that the evidence regarding direct fibroblast activation by stretch is weak and inconsistent, in part because of variability among studies in key experimental conditions that govern the results. Further work is needed to clarify whether, in fact, stretch induces direct activation of cardiac fibroblasts and if so, to elucidate the determining factors to ensure reproducible results. If mechanical load on fibroblasts proves not to be clearly profibrotic by direct actions, other mechanisms like paracrine influences, the effects of systemic mediators and/or the direct consequences of myocardial injury or death, might account for the link between cardiac stretch and fibrosis. Clarity in this area is needed to improve our understanding of AF pathophysiology and assist in therapeutic development.

Procedures for chronic total occlusion: when are they recommended and when not

Coronary chronic total occlusion (CTO) produces an important clinical problem, often treated with medical therapy or coronary artery bypass grafting. Recent clinical studies, both registries and randomized trials, demonstrated that percutaneous coronary interventions (PCI), could provide a valid therapeutic option. Nonetheless, significant reduction in all-cause mortality, cardiac mortality, myocardial infarction, MACE, and MACCE has not been demonstrated in the subgroups analysis of randomized trials. These analyses suggest that PCI for CTO should be reserved for patients with angina or with large areas of the myocardium with reversible ischaemia. Large randomized studies should search for a personalized approach, considering the risks and complexity of PCI in CTO, which should mainly consider the extension of the ischaemia and the viability of the myocardium.

Exosomes in Angiogenesis and Anti-angiogenic Therapy in Cancers

Angiogenesis is the process through which new blood vessels are formed from pre-existing ones. Exosomes are involved in angiogenesis in cancer progression by transporting numerous pro-angiogenic biomolecules like vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMPs), and microRNAs. Exosomes promote angiogenesis by suppressing expression of factor-inhibiting hypoxia-inducible factor 1 (HIF-1). Uptake of tumor-derived exosomes (TEX) by normal endothelial cells activates angiogenic signaling pathways in endothelial cells and stimulates new vessel formation. TEX-driven cross-talk of mesenchymal stem cells (MSCs) with immune cells blocks their anti-tumor activity. Effective inhibition of tumor angiogenesis may arrest tumor progression. Bevacizumab, a VEGF-specific antibody, was the first antiangiogenic agent to enter the clinic. The most important clinical problem associated with cancer therapy using VEGF- or VEFGR-targeting agents is drug resistance. Combined strategies based on angiogenesis inhibitors and immunotherapy effectively enhances therapies in various cancers, but effective treatment requires further research.

URINARY TRACT INFECTIONS IN CHILDREN

The review addresses the main issues related to the rational pharmacotherapy of urinary tract infection (UTI). UTIs are a common and important clinical problem in children. Among UTI causative agents in children are dominated by gram-negative bacteria, E. coli. According to modern clinical guidelines, the leading direction in the treatment of UTI in children is antibiotic therapy, which should be prescribed taking into account the sensitivity of microorganisms. Drugs of choice for UTI in children: cephalosporins or protected aminopenicillins

Central circuit mechanisms of itch

Itch, in particular chronic forms, has been widely recognized as an important clinical problem, but much less is known about the mechanisms of itch in comparison with other sensory modalities such as pain. Recently, considerable progress has been made in dissecting the circuit mechanisms of itch at both the spinal and supraspinal levels. Major components of the spinal neural circuit underlying both chemical and mechanical itch have now been identified, along with the circuits relaying ascending transmission and the descending modulation of itch. In this review, we summarize the progress in elucidating the neural circuit mechanism of itch at spinal and supraspinal levels.