Targeting inflammatory signaling pathways with SGLT2 inhibitors: Insights into cardiovascular health and cardiac cell improvement.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have attracted significant attention for their broader therapeutic impact beyond simply controlling blood sugar levels, particularly in their ability to influence inflammatory pathways. This review delves into the anti-inflammatory properties of SGLT2 inhibitors, with a specific focus on canagliflozin, empagliflozin, and dapagliflozin. One of the key mechanisms through which SGLT2 inhibitors exert their anti-inflammatory effects is by activating AMP-activated protein kinase (AMPK), a crucial regulator of both cellular energy balance and inflammation. Activation of AMPK by these inhibitors leads to the suppression of pro-inflammatory pathways and a decrease in inflammatory mediators. Notably, SGLT2 inhibitors have demonstrated the ability to inhibit the release of cytokines in an AMPK-dependent manner, underscoring their direct influence on inflammatory signaling. Beyond AMPK activation, SGLT2 inhibitors also modulate several other inflammatory pathways, including the NLRP3 inflammasome, expression of Toll-like receptor 4 (TLR-4), and activation of NF-κB (Nuclear factor kappa B). This multifaceted approach contributes to their efficacy in reducing inflammation and managing associated complications in conditions such as diabetes and cardiovascular disorders. Several human and animal studies provide support for the anti-inflammatory effects of SGLT2 inhibitors, demonstrating protective effects on various cardiac cells. Additionally, these inhibitors exhibit direct anti-inflammatory effects by modulating immune cells. Overall, SGLT2 inhibitors emerge as promising therapeutic agents for targeting inflammation in a range of pathological conditions. Further research, particularly focusing on the molecular-level pathways of inflammation, is necessary to fully understand their mechanisms of action and optimize their therapeutic potential in inflammatory diseases.

Pesticide Residues in Vegetables and Fruits from Farmer Markets and Associated Dietary Risks.

The use of pesticides leads to an increase in agricultural production but also causes harmful effects on human health when excessively used. For safe consumption, pesticide residues should be below the maximum residual limits (MRLs). In this study, the residual levels of pesticides in vegetables and fruits collected from farmers' markets in Sharkia Governorate, Egypt were investigated using LC-MS/MS and GC-MS/MS. A total number of 40 pesticides were detected in the tested vegetable and fruit samples. Insecticides were the highest group in detection frequency with 85% and 69% appearance in vegetables and fruits, respectively. Cucumber and apple samples were found to have the highest number of pesticide residues. The mean residue levels ranged from 7 to 951 µg kg-1 (in vegetable samples) and from 8 to 775 µg kg-1 (in fruit samples). It was found that 35 (40.7%) out of 86 pesticide residues detected in vegetables and 35 (38.9%) out of 90 pesticide residues detected in fruits exceeded MRLs. Results for lambda-cyhalothrin, fipronil, dimothoate, and omethoate in spinach, zucchini, kaki, and strawberry, respectively, can cause acute or chronic risks when consumed at 0.1 and 0.2 kg day-1. Therefore, it is necessary for food safety and security to continuously monitor pesticide residues in fruits and vegetables in markets.

Insulin-Induced Edema in a Patient with Type 2 Diabetes Mellitus.

BACKGROUND The strong association between type 2 diabetes and obesity has been well recognized. Insulin treatment is usually needed at some point in the treatment of patients with type 2 diabetes and obesity to achieve the targeted glycemic control goal. CASE REPORT A 35-year-old woman who had gastric banding for morbid obesity 1 year prior presented to the outpatient clinic with recent onset of shortness of breath and bilateral ankle edema, which were thought to be of cardiac origin. Band slippage occurred a few months after the procedure, and the patient gained weight rapidly thereafter. She had been diagnosed with type 2 diabetes mellitus 8 years earlier, which was treated with oral hypoglycemic medication. Thyroid function tests done 4 months prior to her current presentation revealed normal results. A cardiac assessment showed normal cardiac function with no evidence of heart failure. Repeated thyroid function testing showed new-onset subclinical hypothyroidism. The patient had started insulin therapy 2 weeks before her current presentation, which was probably the main cause of her edema. While continuing insulin, the patient's general condition improved with diuretics therapy, following which she had gastric bypass surgery. CONCLUSIONS Insulin-induced edema is an under-diagnosed problem. It should be considered whenever a patient with uncontrolled diabetes develops rapid body swelling after initiation of insulin therapy. Rigorous research is needed to explore the pathophysiology, prevalence, and treatment of insulin-induced edema.

Polyphenolic extracts from pomegranate and watermelon wastes as substrate to fabricate sustainable silver nanoparticles with larvicidal effect against Spodoptera littoralis.

The agricultural wastes adversely affect the environment; however, they are rich in polyphenols; therefore, this study aimed to employ polyphenol-enriched waste extracts for silver nanoparticles synthesis, and study the larvicidal activity of silver nanoparticles fabricated by pomegranate and watermelon peels extracts (PPAgNPs and WPAgNPs) against all larval instars of Spodoptera littoralis. The polyphenol profile of pomegranate and watermelon peel extracts (PP and WP) and silver nanoparticles was detected by HPLC. The antioxidant activity was estimated by DPPH, and FARP assays and the antimicrobial activity was evaluated by disc assay. The Larvicidal activity of AgNPs against Egyptian leaf worm was performed by dipping technique. The obtained AgNPs were spherical with size ranged 15-85 nm and capped with proteins and polyphenols. The phenolic compounds in silver nanoparticles increased about extracts; therefore, they have the best performance in antioxidant/reducing activity, and inhibit the growth of tested bacteria and yeast. The PPAgNPs were the most effective against the first instar larvae instar (LC50 = 68.32 µg/ml), followed by pomegranate extract with (LC50 = 2852 µg/ml). The results indicated that obvious increase in polyphenols content in silver nanoparticles enhance their larvicidal effect and increasing mortality of 1st larval of S. littoralis Egyptian leafworms causing additive effect and synergism. We recommend recycling phenolic enriched agricultural wastes in producing green silver nanoprticles to control cotton leafworm that causes economic loses to crops.

Toll-like receptor-2 Arg753Gln and Arg677Trp polymorphisms and susceptibility to pulmonary and peritoneal tuberculosis.

Recent evidence suggests that toll-like receptor-2 (TLR2) is important for host defense against Mycobacterium tuberculosis (MTB). TLR2 polymorphisms have shown significant impact on susceptibility or resistance to tuberculosis (TB). This case-control study aims to determine the influence of TLR2 (Arg753Gln and Arg677Trp) polymorphisms on the susceptibility to develop pulmonary or peritoneal TB. Genotyping of TLR2 (Arg753Gln and Arg677Trp) polymorphisms was carried out on 52 patients with pulmonary TB, 44 patients with peritoneal TB, and 50 healthy controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). There was a significant association between the GA genotype (heterozygous mutant) of TLR2 Arg753Gln polymorphism and the risk of infection with pulmonary TB (p = 0.003, OR = 4.83) and TB peritonitis (p = 0.003, OR = 6.2). Differences in the genotype frequencies of TLR2 Arg677Trp polymorphisms between patients with pulmonary or peritoneal TB and healthy controls were not detected. GA753 TLR2 polymorphism may play a role in the susceptibility to pulmonary and peritoneal TB infection. Further studies on a large number of ethnically diverse patient cohorts may help to confirm the possible effect of these polymorphisms on the susceptibility to pulmonary and peritoneal TB.

Noncomplicated Excision of a Mobile Pedunculated Septal Hemangioma of the Left Ventricle.

BACKGROUND Cardiac tumors are quite rare, and differential diagnosis of them is challenging. CASE REPORT A young lady with a history of palpitations, dyspnea, and fatigue was proven by transthoracic echocardiography and cardiac magnetic resonance imaging to have a mobile left ventricular mass with rounded contour attached to the mid-part of the interventricular septum. The mass was approached via a posterior inter-atrial approach to avoid left ventriculotomy and provide adequate exposure to completely excise the tumor and control its pedicle with minimal cardiac trauma. Histological examination of the mass was diagnostic of capillary and sinusoidal hemangioma. CONCLUSIONS Complete excision of cardiac hemangioma is recommended once it is diagnosed, for histopathologic diagnosis and because of the possibility of serious complications.

Association between left atrial appendage morphology evaluated by trans-esophageal echocardiography and ischemic cerebral stroke in patients with atrial fibrillation.

The left atrial appendage (LAA) represents one of the major sources of cardiac thrombi responsible for embolic stroke in patients with atrial fibrillation (AF). The aim of the present study was to evaluate LAA structure and functions by transesophageal echocardiography (TEE) in patients with AF to investigate the possible association between the different LAA morphologies and the patients' history of ischemic cerebral stroke. We included 50 patients with non-valvular AF (29 chronic, 21 paroxysmal), 24 patients (13 men) without stroke; and 26 patients (9 men) with a history of ischemic stroke. All patients underwent TEE evaluation of LAA morphology and functions. Compared to patients without stroke, patients with ischemic stroke had significantly higher CHADS2 scores (4.19 ± 0.89 versus 1.67 ± 1.13; P < 0.001) and C-reactive protein levels (8.3 ± 1.6 versus 7.6 ± 0.83 mg/L; P = 0.023), and lower peak filling (21.7 ± 11.3 versus 31.2 ± 9.5 cm/second; P = 0.033) and emptying (22.2 ± 9.7 versus 33.4 ± 13.4 cm/second, P = 0.030) velocities. Triangular LAA morphology had a higher prevalence in patients with stroke (36% versus 12% in non-stroke group); and in half of them an LAA thrombus was present. LAA thrombi were detected in 9 patients (18%) with stroke and in 5 patients (10%) without stroke. On multivariate logistic regression analysis, age (OR = 1.202 [1.042-1.585]; P = 0.041), LAA orifice diameter (OR = 1.275 [1.102-1.748]; P = 0.028), and triangular LAA morphology (OR = 4.53 [1.629-8.381]; P = 0.011) were significantly and independently associated with ischemic stroke in AF patients. LAA morphology evaluated by TEE may be useful for predicting ischemic cerebral stroke in patients with non-valvular AF, especially in those with a low CHADS2 score.

A huge thrombosed pulmonary artery aneurysm without pulmonary hypertension in a patient with hepatosplenic schistosomiasis.

BACKGROUND: We herein report a case of huge pulmonary artery aneurysm in a 55-year-old male farmer from the Nile delta (Lower-Egypt), mostly due to infestation with Schistosoma mansoni, which is the parasite causing hepatosplenic schistosomiasis. CASE REPORT: This male patient was admitted with a month-long history of progressive shortness of breath, 2-month history of fever, and a cough with mucoid sputum for 10 days. On examination, he had normal temperature and blood pressure, but he had tachypnea, tachycardia, and congested neck veins. Electrocardiography showed multifocal atrial tachycardia and right bundle branch block. CONCLUSIONS: The present case is unique in that it shows the presence of a huge pulmonary artery aneurysm despite the absence of pulmonary hypertension.

Spontaneous hemarthrosis following fibrinolytic therapy for acute myocardial infarction: a case report and literature review.

Background Despite the widespread use of fibrinolytic therapy and the numerous reports on its bleeding complications, spontaneous hemarthrosis following fibrinolytic therapy is quite rare. Case Report We describe in this report a patient with no previous history of articular disease who developed a spontaneous right knee bloody effusion following fibrinolytic therapy using rt-PA for acute ST-elevation myocardial infarction. Furthermore, we provide a review of all cases of spontaneous hemarthrosis documented so far in the literature. Conclusions Several pre-existing joint diseases may predispose to hemarthrosis following fibrinolytic therapy, even in patients who deny previous or current articular disorders. Therefore, hemorrhage should be considered in the differential diagnosis of mono-arthritis following fibrinolytic therapy for STEMI.

A novel technique for multi-track percutaneous balloon mitral valvoplasty.

Percutaneous balloon mitral valvoplasty (PBMV) has become the treatment of choice for severe pliable rheumatic mitral stenosis. The multi-track system is a recent variation of the double-balloon technique and is easier owing to the use of a monorail balloon and a simple, single-guidewire approach. In the present study, we used the double-coil Inoue metal wire with a multi-track balloon instead of the conventional multi-track wire. We studied 62 consecutive patients (55 females) with significant symptomatic rheumatic mitral valve stenosis who underwent multi-track PBMV. Patients were randomized into 2 groups: the first group included 32 patients treated with the novel multi-track technique using the double-coil Inoue metal wire, and the second group included 30 patients treated with the conventional multi-track technique using a balloon endhole catheter and multi-track 0.035 inch stiff wire. None of the patients had cardiac tamponade, systemic thromboembolism, or any groin complications. No statistically significant differences were found between the 2 groups regarding any of the studied variables. There were no in-hospital deaths or complications necessitating emergent cardiac surgery in either group. In conclusion, this new technique with the double-coil Inoue metal wire achieves the double benefit of being as safe as (and indeed easier than) the conventional technique, and it utilizes fewer materials, making the multi-track system more cost-effective.

Use of adenosine deaminase measurements and QuantiFERON in the rapid diagnosis of tuberculous peritonitis.

Peritoneal tuberculosis (TB) is a considerable problem in certain developing nations. Current diagnostic tests for peritoneal TB are difficult and time-consuming. This study aimed to determine the effectiveness of an adenosine deaminase (ADA) assay and the QuantiFERON-Gold (QFT-G) assay in the rapid diagnosis of TB peritonitis. Forty-one patients with a presumptive diagnosis of TB peritonitis with ascites were admitted to Mansoura University Hospital and included in the study. Ascitic fluid and blood samples were collected from each patient. Fluid samples were examined biochemically (protein concentration), cytologically (white blood cell count) and microbiologically (Ziehl-Neelsen stain and TB culture in Löwenstein-Jensen media), and ADA levels were determined using colorimetry. Interferon-γ levels in whole-blood samples were measured using the QFT-G assay. Fourteen (34 %) patients received a final clinical diagnosis of TB peritonitis; these patients were subclassified as definite (positive culture for Mycobacterium tuberculosis; eight patients), highly probable (four patients) and probable (two patients) for TB peritonitis. Of the 14 patients with a final clinical diagnosis of TB peritonitis, 3 (21 %) tested positive using an acid-fast bacilli smear, which showed a sensitivity of 21 % and a specificity of 100 %. A receiver operating characteristic curve showed that a cut-off value of 35 IU l(-1) for the ADA level produced the best results as a diagnostic test for TB peritonitis, yielding the following parameter values: sensitivity 100 %, specificity 92.6 %, positive predictive value (PPV) 87.5 % and negative predictive value (NPV) 100 %. The QFT-G assay yielded the following values: sensitivity 92.9 %, specificity 100 %, PPV 100 % and NPV 96.4 %. The ADA and QFT-G assays might be used to rapidly diagnose TB peritonitis and initiate prompt treatment while waiting for a final diagnosis using the standard culture approach.

Force-frequency relationship as a predictor of long-term prognosis in patients with heart diseases.

Adequate evaluation of the nature of the residual failing myocardium, as well as the severity of myocardial injury, is important for managing patients with heart failure. The aim of this study was to investigate the myocardial function and the prognosis of patients with heart diseases using the force-frequency relationship (FFR). We enrolled 76 patients with sinus rhythm who had miscellaneous heart diseases and performed incremental right atrial pacing at the time of diagnostic cardiac catheterization. The first derivatives of left ventricular pressure (dP/dt) were recorded using a micro manometer-tipped catheter during the study. To represent properties of FFR, two parameters-the peak force rate (PFR) and force gain (FG)-were estimated. PFR was defined as the heart rate at which dP/dt became maximum. FG was defined as the difference between dP/dt at PFR and dP/dt at the basal heart rate. FG decreased as the severity of left ventricular (LV) dysfunction increased (372.0 ± 110.7, 209.5 ± 29.1 and 116.3 ± 13.1 mmHg/s for normal LV function, mild LV dysfunction and severe LV dysfunction groups, P < 0.05, respectively). PFR correlated with cardiac index (r = 0.375, P = 0.001). FG correlated with LV end systolic volume index (r = -0.297, P = 0.010) and LV ejection fraction (r = 0.539, P < 0.001). Furthermore, pulmonary arterial wedge pressure [hazard ratio (HR) 1.126, P < 0.01] and FG (HR 0.992, P = 0.061) tended to be independent predictors for cardiovascular death. Analysis of FFR, especially FG, seems to be useful to evaluate the nature of the failing myocardium and the prognosis of patients with heart diseases.

Microvascular angina. The possible role of inflammation, uric acid, and endothelial dysfunction.

Microvascular angina is a condition characterized by angina-like chest pain and normal coronary angiography. Endothelial dysfunction and systemic inflammation with elevated serum high-sensitive C-reactive protein (hsCRP) levels play a role in its pathogenesis. This study aimed to explore the possible relation between CRP, brachial flow-mediated dilatation (FMD), and microvascular angina.We included 21 patients with attacks of chest pain diagnosed as microvascular angina (study group) and 10 normal asymptomatic subjects (control group). Patients and controls were thoroughly examined clinically and by echocardiography, electrocardiography, and brachial FMD (using external brachial ultrasonography). Serum hsCRP and uric acid levels were assessed in all subjects.A significantly higher mean hsCRP level was found in the study group compared to controls (11.5+/-3.8 versus 3.34+/-1.5 mg/L; P<0.001). FMD of the brachial artery showed significant impairment in patients with microvascular angina compared to controls (0.16+/-0.06 versus 0.76+/-0.09 mm; P<0.001). There were significantly higher total cholesterol (196.1+/-44.4 versus 159.8+/-14.5 mg/dL; P=0.018) and triglyceride levels (185.0+/-103.2 versus 113.0+/-17.6 mg/dL; P=0.038) in the patients compared to controls; but there was a statistically insignificant difference in mean serum uric acid levels between these two groups. There were no significant correlations between the brachial FMD and any of the clinical variables studied (apart from ankle/brachial index). Microvascular angina may have an inflammatory element (reflected as a higher serum hsCRP level), together with a contribution by endothelial dysfunction (reflected as impaired brachial artery FMD); while serum uric acid is possibly not associated with microvascular angina.

Evaluation of channel function after alteration of amino acid residues at the pore center of KCNQ1 channel.

The effect of the electrical charge or the size of the amino acid residue at the pore center of a slowly activation component of the delayed rectifier potassium channel: KCNQ1 was studied. K(+) currents were measured after transfection of one of four KCNQ1 mutants: substituting Isoleucine with Lysine, Glutamate, Valine or Glycine and then transfected in COS-7 cells. Both the negatively- and positive charged residue I313K and I313E showed a loss of function when expressed alone and a dominant negative suppression when co-expressed with wild type KCNQ1. When the site was substituted with the smallest neutral amino acid residue: I313G, there was a small reduction of current when transfected alone and a gain of function when co-transfected with the wild type. I313V showed no difference from the wild type. Changes of amino acid residue at the pore center of KCNQ1 may alter the channel function but this depends on the electrical charge or the size of amino acid residue.

Evaluation of oxidized low-density lipoprotein in the coronary circulation of patients with coronary artery disease, and its association with percutaneous coronary intervention.

Hereby we report our observations derived from a study of 113 subjects who underwent coronary angiography; of whom 32 were free of coronary lesions (controls) and 27 underwent percutaneous coronary intervention (PCI). In this work, we aimed to investigate the dynamics of oxidized low-density lipoprotein (OxLDL) and the possible effect of PCI on its levels within the coronary circulation of patients with coronary artery disease. We concluded that the mechanical maneuvers applied during PCI may not result in immediate local elevation of OxLDL levels within the coronary circulation of patients with coronary artery disease. Besides, we hypothesized that coronary atheroma might fix OxLDL, especially if mechanically disrupted by PCI.

Health-related quality of life of outpatients with systolic and isolated diastolic dysfunction: Sado Heart Failure Study.

BACKGROUND: The impact of isolated diastolic dysfunction (IDD) and systolic dysfunction (SD) on health-related quality of life (HRQOL) is unknown. METHODS AND RESULTS: To evaluate HRQOL in patients with IDD and SD under treatment, information on outpatients aged 60-84 years was extracted from the records of 4,500 consecutive individuals who underwent echocardiographic examination at Sado General Hospital. The medical records of these patients were reviewed and a questionnaire, including the Medical Outcome Study Short Form 36, was mailed to 71 IDD and 99 SD patients; answers were obtained from 66 and 91 patients, respectively. The HRQOL of patients with cardiac dysfunction was impaired even when echocardiographic parameters improved with treatment. Patients with IDD showed an impairment of HRQOL similar to those with SD. Compared with males, female patients had a larger and more significant reduction in the physical and mental components of the HRQOL score. These scores correlated positively with exercise capacity in patients with IDD or SD. CONCLUSIONS: Impaired HRQOL, in both its mental and physical components, is a serious problem for IDD and SD patients under treatment. Because exercise intolerance may underlie the reduced HRQOL, improving exercise capacity could be an important target for managing outpatients with heart failure.

Comparative analysis of systolic and isolated diastolic dysfunction: Sado heart failure study.

Determining the type of cardiac dysfunction is important for implementing therapeutic strategies and for prognostic insights. We characterized systolic dysfunction (SD) and isolated diastolic dysfunction (IDD) in adults referred for echocardiographic evaluation, and compared their clinical and other characteristics. In the present work, we studied 218 patients (137 males) with cardiac dysfunction (mean age, 66.3 +/- 8.3 years). SD was defined as a left ventricular ejection fraction (LVEF) of < 45%, whereas IDD was defined as a LVEF >or= 45% in addition to the standard Doppler-echocardiography diagnostic criteria for IDD. Approximately 68% of subjects had SD (70% males). The proportions of hypertension, diabetes, and dyslipidemia were 44%, 26%, and 22%, respectively, without significant association with the type of dysfunction. Myocardial infarction (MI) was found in 31% of patients, and was significantly (P < 0.001) more prevalent among SD compared with IDD cases. Cerebral stroke (18%) and malignancy (16%) were significantly associated with IDD (29% versus 13% for SD in the case of stroke, and 26% versus 11% for SD in the case of malignancy; P = 0.008 for each). In multivariately-adjusted logistic regression analysis, the following variables were found to be significantly (P < 0.05) and independently associated with IDD: female gender (odds ratio [OR] = 2.207 [95% CI = 1.302-4.608]), stroke (OR = 2.009 [1.119-3.980]), and malignancy (OR = 2.016 [1.230-4.010]). On the other hand, previous MI (OR = 2.075 [1.769-4.808]) was independently associated with SD. In conclusion, some factors/comorbidities were more likely to associate with IDD (female gender, stroke, and malignancy) or SD (previous MI) when IDD and SD were compared with each other.