360-Degree Perspectives on Obesity.

Alarming statistics show that the number of people affected by excessive weight has surpassed 2 billion, representing approximately 30% of the world's population. The aim of this review is to provide a comprehensive overview of one of the most serious public health problems, considering that obesity requires an integrative approach that takes into account its complex etiology, including genetic, environmental, and lifestyle factors. Only an understanding of the connections between the many contributors to obesity and the synergy between treatment interventions can ensure satisfactory outcomes in reducing obesity. Mechanisms such as oxidative stress, chronic inflammation, and dysbiosis play a crucial role in the pathogenesis of obesity and its associated complications. Compounding factors such as the deleterious effects of stress, the novel challenge posed by the obesogenic digital (food) environment, and the stigma associated with obesity should not be overlooked. Preclinical research in animal models has been instrumental in elucidating these mechanisms, and translation into clinical practice has provided promising therapeutic options, including epigenetic approaches, pharmacotherapy, and bariatric surgery. However, more studies are necessary to discover new compounds that target key metabolic pathways, innovative ways to deliver the drugs, the optimal combinations of lifestyle interventions with allopathic treatments, and, last but not least, emerging biological markers for effective monitoring. With each passing day, the obesity crisis tightens its grip, threatening not only individual lives but also burdening healthcare systems and societies at large. It is high time we took action as we confront the urgent imperative to address this escalating global health challenge head-on.

The Roles of Imaging Biomarkers in the Management of Chronic Neuropathic Pain.

Chronic neuropathic pain (CNP) affects around 10% of the general population and has a significant social, emotional, and economic impact. Current diagnosis techniques rely mainly on patient-reported outcomes and symptoms, which leads to significant diagnostic heterogeneity and subsequent challenges in management and assessment of outcomes. As such, it is necessary to review the approach to a pathology that occurs so frequently, with such burdensome and complex implications. Recent research has shown that imaging methods can detect subtle neuroplastic changes in the central and peripheral nervous system, which can be correlated with neuropathic symptoms and may serve as potential markers. The aim of this paper is to review available imaging methods used for diagnosing and assessing therapeutic efficacy in CNP for both the preclinical and clinical setting. Of course, further research is required to standardize and improve detection accuracy, but available data indicate that imaging is a valuable tool that can impact the management of CNP.

An Overview of the Pharmacokinetics and Pharmacodynamics of Landiolol (an Ultra-Short Acting ß1 Selective Antagonist) in Atrial Fibrillation.

Landiolol is an ultra-short-acting, selective ß1-adrenergic receptor blocker that was originally approved in Japan for the treatment of intraoperative tachyarrhythmias. It has gained attention for its use in the management of tachyarrhythmias and perioperative tachycardia, especially atrial fibrillation for both cardiac and non-cardiac surgeries. It can be the ideal agent for heart rate control due to its high ß1-selectivity, potent negative chronotropic effect, a limited negative inotropic potential, and an ultrashort elimination half-life (around 4 min); moreover, it may have a potential therapeutic effects for sepsis and pediatric patients. Landiolol seems to be superior to other short-acting and selective beta-blockers such as esmolol. This review aims to provide a comprehensive overview of landiolol, a new ultra-short-acting ß1 selective antagonist, including its pharmacology, clinical applications, efficacy, safety profile, and future directions in research and clinical data.

Cystic fibrosis management in pediatric population-from clinical features to personalized therapy.

Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations of the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). In 1949, it's been identified as a monogenic disease and was thought to primarily affect individuals of Northern European descent. It was the most prevalent autosomal recessive disease that shortens life. With the availability of multiple testing methodologies nowadays, there is a chance to create novel and enhanced treatment options. Even in the absence of a high sweat chloride test (SCT) result, the discovery of two causal mutations is diagnostic for cystic fibrosis (CF). For a CF diagnosis, however, at least two positive E sweat chloride tests are still required. In order to achieve early and active intervention to manage cystic fibrosis (CF) and its comorbidities, treatment regimens for pediatric patients should be evaluated, improved, and closely monitored. New developments in the treatment of cystic fibrosis (CF) have led to the development of medications derived from molecules that target the pathogenetic pathway of the illness. These options are very efficient and allow pediatric patients to receive individualized care. However, in order to better direct patient care and enhance patient outcomes, it is crucial to research uncommon CF mutations, which can provide crucial information about the prognosis of the disease and the relationships between genotype and phenotype. To ensure the success of creating novel, safer, and more efficient treatment approaches, a deeper understanding of the pathogeny of the illness is required. In the age of customized medicine, genetic research will be essential to improving patient care and quality of life for those with uncommon mutations.

A Retrospective Clinical Trial Regarding Oral Rehabilitation Diagnosis Strategies Based on Stomatognathic System Pathology.

INTRODUCTION: Orofacial pain is a common occurrence in daily dental practice; it is frequently attributed to temporomandibular dysfunction, one of its major causes, followed by pathology of the salivary glands, without avoiding interference at the level of the pain pathways caused by complications of periodontal pathology. The main objective of this study is to identify an important cause of pain in the oral-maxillofacial territory by quantifying the changes at the salivary glandular level using stereological methods. The secondary objective of the present research is to identify the implications of periodontal changes as a consequence of salivary quantitative and qualitative changes, quantified using periodontal indices, on the balance of the temporomandibular joint, dysfunction of it being an important cause of facial pain and having a profound impact on the complex oral rehabilitation algorithm of each clinical case, a condition evaluated with the analysis of the results of the Souleroy questionnaire. MATERIAL AND METHODS: In a retrospective study, we evaluated the clinical results obtained after applying complex rehabilitation treatment to 35 subjects, 20 women and 15 men with salivary and TMJ dysfunctions, selected between 2020 and 2021 from the Clinic of Maxillofacial Surgery, Iasi. RESULTS AND DISCUSSION: The most common symptoms of temporomandibular disorders (TMDs) that were identified through the Souleroy questionnaire were pain and different types of damage to the masticatory muscles. The most significant changes in elders are reported in the case of serous cells, which reduced their percentage volume from 46.7% to 37.4%. CONCLUSION: As regards stereological analysis in conjunction with histological images, there were significant changes in diameters, perimeters, and longitudinal axes in the adult patients as opposed to the elderly patients, which were also influenced by the type of pathology at this level. The scores recorded on the diagnostic Souleroy scale indicated a large number of patients with low efficiency and maximum stress levels: 20.0% in level 1, 25.7% in level 2, and 25.7% in level 3.

Mesenchymal Stem Cell-Derived Exosomes Modulate Angiogenesis in Gastric Cancer.

Individualized gastric cancer (GC) treatment aims at providing targeted therapies that translate the latest research into improved management strategies. Extracellular vesicle microRNAs have been proposed as biomarkers for GC prognosis. Helicobacter pylori infection influences the therapeutic response to and the drivers of malignant changes in chronic gastritis. The successful use of transplanted mesenchymal stem cells (MSCs) for gastric ulcer healing has raised interest in studying their effects on tumor neovascularization and in potential antiangiogenic therapies that could use mesenchymal stem cell secretion into extracellular vesicles-such as exosomes-in GC cells. The use of MSCs isolated from bone marrow in order to achieve angiogenic modulation in the tumor microenvironment could exploit the inherent migration of MSCs into GC tissues. Bone marrow-derived MSCs naturally present in the stomach have been reported to carry a malignancy risk, but their effect in GC is still being researched. The pro- and antiangiogenic effects of MSCs derived from various sources complement their role in immune regulation and tissue regeneration and provide further understanding into the heterogeneous biology of GC, the aberrant morphology of tumor vasculature and the mechanisms of resistance to antiangiogenic drugs.

Current Approaches in the Multimodal Management of Asthma in Adolescents-From Pharmacology to Personalized Therapy.

Asthma and adolescence are two sensitive points and are difficult to manage when they coexist. The first is a chronic respiratory condition, with frequent onset in early childhood (between 3 and 5 years), which can improve or worsen with age. Adolescence is the period between childhood and adulthood (12-19 years), marked by various internal and external conflicts and a limited capacity to understand and accept any aspect that is delimited by the pattern of the social circle (of the entourage) frequented by the individual. Therefore, the clinician is faced with multiple attempts regarding the management of asthma encountered during the adolescent period, starting from the individualization of the therapy to the control of compliance (which depends equally on the adverse reactions, quality of life offered and support of the close circle) and the social integration of the subject, communication probably having a more important role in the monitoring and evolution of the condition than the preference for a certain therapeutic scheme. Current statistics draw attention to the increase in morbidity and mortality among children with bronchial asthma, an aspect demonstrated by the numerous hospitalizations recorded, due either to an escalation in the severity of this pathology or to faulty management. The purpose of this article is to review the delicate aspects in terms of controlling symptoms and maintaining a high quality of life among teenagers.

The Anticancer Potential of Plant-Derived Nutraceuticals via the Modulation of Gene Expression.

Current studies show that approximately one-third of all cancer-related deaths are linked to diet and several cancer forms are preventable with balanced nutrition, due to dietary compounds being able to reverse epigenetic abnormalities. An appropriate diet in cancer patients can lead to changes in gene expression and enhance the efficacy of therapy. It has been demonstrated that nutraceuticals can act as powerful antioxidants at the cellular level as well as anticarcinogenic agents. This review is focused on the best studies on worldwide-available plant-derived nutraceuticals: curcumin, resveratrol, sulforaphane, indole-3-carbinol, quercetin, astaxanthin, epigallocatechin-3-gallate, and lycopene. These compounds have an enhanced effect on epigenetic changes such as histone modification via HDAC (histone deacetylase), HAT (histone acetyltransferase) inhibition, DNMT (DNA methyltransferase) inhibition, and non-coding RNA expression. All of these nutraceuticals are reported to positively modulate the epigenome, reducing cancer incidence. Furthermore, the current review addresses the issue of the low bioavailability of nutraceuticals and how to overcome the drawbacks related to their oral administration. Understanding the mechanisms by which nutraceuticals influence gene expression will allow their incorporation into an "epigenetic diet" that could be further capitalized on in the therapy of cancer.

An Immunoenzymatic Method for the Determination of Ochratoxin A in Biological Liquids (Colostrum and Cow's Milk).

Ochratoxins are mycotoxins that have been extensively studied lately due to the multiple toxic effects such as nephrotoxicity, hepatotoxicity, and carcinogenicity. These toxins contaminate plant and animal foods and after ingestion they reach into body fluids. The method of competitive direct enzyme immunoassay, in the solid phase, was validated through the determination of specific parameters (performance, linearity, recovery percentage, limit of detection, limit of quantification). The validated method was used to determine ochratoxin A in colostrum and cow's milk. The method applied for the determination of ochratoxin A was linear for the concentration range of 0.0-0.5 ng/mL, the value for the regression coefficient (r) was 0.9838. Ochratoxin A was present in 91.67% of the colostrum and in 93.33% of cow's milk samples. The linearity of the method, demonstrated for very low concentrations of analyte, the detection limit as well as the limit of quantification recommend the method for the determinations of micro-pollutants from foods, including biological fluids.

Comparative Study Regarding the Adherence to the Mediterranean Diet and the Eating Habits of Two Groups-The Romanian Children and Adolescents Living in Nord-West of Romania and Their Romanian Counterparts Living in Italy.

BACKGROUND: The Mediterranean diet (MD) is associated with significant health benefits, including prevention of noncommunicable diseases (NCDs). Given the important migratory flow from Romania to Italy in recent decades, this study seeks to evaluate the differences between the nutritional habits of Romanian children and adolescents in Romania compared with those of Romanian children who moved to Italy or were born in Italy from both Romanian parents. METHOD: To assess adherence to MD, parents of Romanian children in Romania (RCR) and Romanian children in Italy (RCI) answered questions from an adapted version of the KIDMED test. RESULTS: The results show that the high KIDMED index among RCI is significantly higher than the same index among RCR (68.09 versus 17.76, p < 0.05). RCR obtained a higher KIDMED score on different items: they had a lower consumption of fast food and sweets but an increased consumption of nuts, yogurts, and cheese. CONCLUSIONS: RCI have a better adherence to MD, but, at the same time, they are more exposed to westernized diet and practice less physical activity. Nutrition education is an important tool for improving health outcome.

The protective effect of montelukast sodium on carbon tetrachloride induced hepatopathy in rat.

AIM: This study investigates the effects of montelukast sodium (MK) (CysLTLT1 receptor antagonist) on CCl(4)induced hepatopathy on rat. MATERIAL AND METHODS: We worked on 4 groups of 10 Wistar male rats each. The groups received as follows: group I (control group) - saline, group II - MK 5mg/kg/day i.p. for 5 days, group III - MK 5mg/kg/day i.p., 1 day prior to and 4 days concomitantly with CCl(4) p.o., 0.3ml/Kg/day and group IV - CCl(4), p.o., 0.3ml/Kg/day for 4 days. One day after the last administration, samples of blood were taken and alanine aminotransferase (ALT), total bilirubin (TB), direct bilirubin (DB), malondialdehyde (MDA), catalase (CAT) as well as total antioxidant capacity (TAC) were determined. The histopathological exam was performed. We also determined superoxide dismutase (SOD), MDA, CAT and GSH in liver homogenate. RESULTS: Compared to group IV, group III exhibited statistically significant lower levels of ALT (318+/-15.75 versus 203.14+/-10.28 UI, p<0.0001), TB (3.16+/-0.30 versus 1.99+/-0.08mg/dl, p<0.0001), MDA in blood and in liver homogenate (4.98+/-1.71 versus 2.15+/-1.18nmol/ml, p=0.0004) and higher levels of SOD and CAT. Histopathologically, group IV presented important macro- and micro-vesicular hepatic steatosis and group III preserved lobular histoarchitecture and had less severe cellular lesions. CONCLUSION: MK exhibits a partial hepatoprotective effect on rats treated with CCl(4).

Effect of apitherapy products against carbon tetrachloride-induced toxicity in Wistar rats.

The present paper aimed to evaluate the influence of apitherapy diet in Wistar rats with carbon tetrachloride induced hepatotoxicity, by the means of biochemical determinations and histopathological changes of liver, spleen, pancreas and testicular tissue. The experiment was carried out on six groups of male Wistar rats. Hepatic lesions were induced by intraperitoneal injection of carbon tetrachloride (dissolved in paraffin oil, 10% solution), 2 mL per 100 g, every two days, for two weeks. Hepatoprotection was achieved with two-apitherapy diet formulations (containing honey, pollen, propolis, Apilarnil, with/without royal jelly), that have been administered for six up to nine weeks. The biochemical results revealed that the two-apitherapy diet formulations had a positive effect improving the enzymatic, lipid, and protein profiles, coagulation, mineral parameters and also the bilirubin levels, after six weeks of treatment. The histopathological results demonstrated the benefit of the two-apitherapy diet formulations on reducing the toxicity of liver, spleen and pancreas in laboratory animals, after six and nine weeks, respectively. In conclusion, apitherapy products have a hepatoprotective effect in carbon tetrachloride-induced hepatopathy.

Vasorelaxant effects and mechanisms of action of Heracleum sphondylium L. (Apiaceae) in rat thoracic aorta.

ETHNOPHARMACOLOGICAL RELEVANCE: Aerial parts of Heracleum sphondylium L. (HS) are used in traditional medicine to treat hypertension. To provide pharmacological basis for this use, we investigated the vasorelaxant effects of a dichloromethane extract of HS (HSDE) and the mechanisms involved. MATERIALS AND METHODS: Activity of HSDE was evaluated on rat isolated thoracic aortic rings. RESULTS: HSDE induced vasorelaxation in phenylephrine (PE, 10(-6)mol/L) and high KCl-(6×10(-2)mol/L) pre-contracted aortic rings that was independent on the presence of endothelium. HSDE markedly decreased extracellular Ca(2+)-induced contraction in high-KCl and PE pre-challenged rings. It also inhibited the intracellular Ca(2+) release sensitive to PE (10(-6)M). The relaxant effect of HSDE were blunted by 4-amino-pyridine (4-AP, 10(-3)mol/L), an inhibitor of voltage-dependent K(+) channels. CONCLUSION: Our results provide the first evidence that a dichloromethane extract of Heracleum sphondylium L. exhibits vasorelaxant properties through endothelium-independent mechanisms involving the inhibition of Ca(2+) mobilization and changes in Kv channel conductances. These data argue for its use as antihypertensive therapy in traditional medicine.

Estimation of ochratoxin A in the human blood of Romanian population.

UNLABELLED: Ochratoxin A (OTA) is a toxic secondary metabolite of fungi belonging to the Aspergillus and Penicillium genera, its presence in human blood being the primary indicator of exposure. AIM: In the present study we determined OTA in 38 blood samples collected from healthy Romanian subjects of both genders. MATERIAL AND METHODS: The OTA was determined through the direct, competitive, solid-phase immunoenzymatic method; the minimum quantification limit for determining OTA in serum samples was 0.0289 ng/mL. RESULTS: The positive sample percentage was 100%. OTA concentrations varied between < 0.04 ng/mL and 1 ng/mL. There were no significant differences between OTA concentrations in men versus women (0.24 +/- 0.20 ng/mL versus 0.17 +/- 0.15 ng/mL, p = 0.3527). CONCLUSIONS: The analyzed blood samples exhibit a very high degree of exposure to OTA, but in only approximately 10% of the subjects exceeded 0.5 ng/mL, considered the threshold for OTA-induced renal pathology.

Food-drug interactions: grapefruit juice.

Food-drug interactions are increasingly recognized as important clinical events which may change significantly the bioavailability of oral administrated drugs. Grapefruit juice (GFJ) demonstrated multiple interactions with drugs leading to loss of the therapeutic effects or increased side-effects. GFJ decreases pre-systemic metabolism through a) competitive or mechanism-based inhibition of gut wall CYP3A4 isoenzymes and b) P-glycoprotein (P-gp), c) multidrug resistance protein-2 (MRP2) or d) organic anion-transporting polypeptide (OATP) inhibition. Although, GFJ presents high amounts of flavonoids (e.g. naringin, naringenin), furanocoumarins (e.g. 6',7'-dihydroxybergamottin, bergamottin) are the main chemicals involved in the pharmacokinetic interactions. As compounds of GFJ show additive or synergistic effects, all the major furanocoumarins are necessary for the maximal inhibitory effect. Also, related citrus fruits (sweeties, pummelo and sour orange) or various plants containing furanocoumarins may present pharmacological interactions, yet to be discovered.

Protective effects of selenium on acrylamide toxicity in the liver of the rat. Effects on the oxidative stress.

UNLABELLED: Acrylamide (AA), obtained for the first time by Moureu in Germany in 1893, is presently used as polyacrylamide in water treatment and wastewater treatment, paper and pulp processing, mineral processing, crude-oil production processes. Acrylamide is a chemical product formed when frying, roasting, grilling or baking carbohydrate-rich foods at temperatures above 120 degrees C. Acrylamide is thus found in a number of foods, such as bread, crisps, French fries and coffee. Tobacco smoking also generates substantial amounts of acrylamide. Acrylamide administration is associated with significant increase of oxidative stress parameters; acrylamide caused disturbances in the oxidative status and enzyme activities and the effect was pronounced with the high doses. MATERIAL AND METHODS: This study investigates the effect of selenium (as sodium selenite and as a selenium dietary supplements--Celnium) on the oxidative stress in Wistar rats which received high doses of acrylamide. RESULTS: The administration of sodium selenite and selenium dietary supplements (Celnium) significantly increased GSH and GPx levels and decreased MDA compared to group which received only acrylamide. CONCLUSIONS: Our results show that sodium selenite and selenium dietary supplements (Celnium) can partially prevent the biochemical changes in the liver of the rats which received high doses of acrylamide.

[Flavonoids--bioactive compounds in fruits juice]. / Flavonoidele--componente bioactive din sucuri de fructe.

UNLABELLED: Since 1989, grapefruit juice is reported to modify, with clinical implications, the pharmacokinetic of a series of drugs such as calcium channel blockers that are dihydropyridine derivates and/or some HMGCoA reductase inhibitors. All these drugs are metabolized to a large extent by the most abundant human isoform of cytochrome P450, CYP3A4. Grapefruit inhibits the cytochrome P450 3A4 enzyme system responsible for the oxidative metabolism of many orally administered drugs. The most important compounds of GFJ considered to be involved in the pharmacokinetic interaction are flavonoids (naringin, naringenin, narirutin, quercetin, kaempferol, hesperidin, neohesperidin, didymin, and poncirin), furanocoumarins (6',7'-dihydroxy-bergamottin, bergamottin, bergamottin-6',7'-epoxide, bergapten, epoxy-bergamottin) and sesquiterpens (noot-katone). MATERIAL AND METHOD: The experimental researches had as object the comparative study of total content of flavonoidic compounds, like naringin in different fruit juices: citric fruit (white, pink and red grapefruit), apples, pears--industrial or laboratory prepared juices (by squeezing). They praised a different content in flavonoidic compounds for citric and for the rest of analyzed fruits. RESULTS: For grapefruit juices the concentrations in flavonoidic compounds are higher in total fruit juice: 143.86 mg/100 mL in red, 131.47 mg/100 mL in pink and 84.21 mg/100 mL in white grapefruit juice. In juice prepared from fruit pulp, the concentrations were 81.92 mg/100 mL, 108.23 mg/100 mL and 65.76 mg/100 mL, respectively. The content in naringin, the most important flavanone in citrus fruit, varied between 1.98 and 51.2 mg/100 mL juice.

Grapefruit juice--drug interactions: importance for pharmacotherapy.

In spite of known health benefits of grapefruit juice, its consumption in combination with drugs requires caution. The drugs most susceptible to pharmacokinetic interactions with clinical significance are those with narrow therapeutic index and low bioavailability due to important first-pass metabolism. Most vulnerable populations are elderly, cirrhotics, subjects with genetic polymorphisms and individuals taking other CYP3A4 inhibitors. The major drug classes that have been reported to present interactions with grapefruit juice are antiallergics, antibiotics, antimalaria drugs, anxiolytics, calcium channel blockers, HIV protease inhibitors, HMG-CoA reductase inhibitors; the degree of pharmacokinetic interaction varies among the compounds of the same class.

New method for determination of dydrogesterone in human plasma for therapeutic drug monitoring in gynecological disorders.

UNLABELLED: A new simple, sensitive and selective liquid chromatography coupled with mass spectrometry (LC/MS) method for quantification of dydrogesterone in human plasma was validated. MATERIAL AND METHOD: The analytes was eluted in 1.3 minutes on a reversed phase column (Zorbax SB-C18, 100 mm x 3.0 mm I.D., 3.5 microm) under isocratic conditions using a mobile phase of a 20 : 80 (v/v) mixture of ammonium acetate 1 mM and acetonitrile. The flow rate was 1 mL/min at the column temperature of 35 degrees C. The detection of the analyte was in MS/ MS mode using an atmospheric pressure chemical ionization source (APCI+, m/z 313 > m/z 295). The sample preparation was very simple and rapid and consisted in plasma protein precipitation from 0.2 mL plasma using 0.6 mL methanol. RESULTS: Calibration curves were generated over the range of 5-150 ng/mL with values for coefficient of determination greater than 0.997 and by using a weighted (1/y) linear regression. The values of precision and accuracy were less than 12.5% and 7.5%, respectively, both for within- and between-run analysis. The mean recovery of the analyte was 99.8%. This is the first reported method for analysis dydrogesterone in human plasma that uses protein precipitation as sample processing procedure. The validated LC/MS method could be applied for determination of dydrogesterone in human plasma for therapeutic drug monitoring in gynecological disorders.