Approaches based on natural products and miRNAs in pituitary adenomas: unveiling therapeutic intervention.

Pituitary adenomas (PAs) are tumors originating in the pituitary gland, a small gland located at the base of the brain. They are the most common type of pituitary tumor, affecting approximately 1 in 10 people over their lifetime. Common symptoms include headaches, vision problems, hormonal imbalances, and weight changes. Treatment options depend on the type and size of the adenoma and may consist of medication, surgery, radiation therapy, or a combination. PAs are typically benign and slow-growing, but they can cause significant health issues if left untreated. Proper diagnosis and management by an experienced multidisciplinary team is important for achieving the best outcomes. Natural compounds like celastrol, curcumin, quercetin, apigenin, resveratrol, epigallocatechin gallate (EGCG), and genistein have shown the ability to inhibit cell growth, promote cell death, and suppress hormone activity in pituitary tumor cells, suggesting their potential as alternative or complementary treatments for PAs. MicroRNAs (miRNAs) are a kind of tiny RNA molecules that do not code for proteins and have a vital function in controlling gene expression. These 21-23 nucleotide-long molecules regulate gene expression by binding to complementary sequences in mRNA molecules, leading to mRNA degradation. miRNAs participate in a wide range of biological activities, including apoptosis, metastasis, differentiation, and proliferation. The research indicates that miRNAs play a crucial role in the pathogenesis, therapeutic approaches, diagnosis, and prognosis of PAs. This review article will provide a comprehensive analysis of the current understanding of the efficacy of naturally derived anti-cancer agents in the treatment of PAs. Furthermore, the study provides a comprehensive assessment of the miRNAs in PAs, their role in the development of PAs, and their potential application in the treatment of the condition.

Successful Late Repair of Truncus Arteriosus: A Single Center Experience.

Background: Truncus arteriosus is a rare congenital heart defect resulting from the failure of the truncus arteriosus to divide during fetal development. It leads to a single outflow tract from the heart and, if left untreated, can be fatal. Late presentation and repair can also increase the risk of pulmonary hypertensive crises, which can lead to morbidity and mortality after repair. Methods: We performed a retrospective study examining outcomes of late-presenting patients who were repaired for this anomaly at our institution. Results: We identified seven patients who underwent late repair of truncus arteriosus who were 3 to 11 years of age. There were six females and one male. Postoperatively, all patients showed improvement in symptoms and hemodynamic parameters, with no reported mortality. The median duration of stay in the intensive care unit was nine days and with a range from 3 to 18 days, while the median hospital stay was 29 days with a range from 21 to 60 days. Conclusion: These findings highlight the potential for successful outcomes even in cases of delayed diagnosis.

A novel triad for the diagnosis of endometriosis, the short anogenital distance combines with high endometrial BCL2 and low endometrial FASL.

OBJECTIVE: To investigate the anogenital distance from the upper verge of the anus to the posterior fourchette (AGDAF), FASL, and BCL2 combination as a reliable and non-invasive tool for the diagnosis of endometriosis. METHODS: This study included 100 women with endometriosis and 50 women without endometriosis as the control group. All cases underwent history taking, body mass index (BMI) measurement, AGD measurement, and FASL and BCL2 immunohistochemical staining of the eutopic endometrial tissue. RESULTS: This study included 150 women divided into endometriosis and control groups. Endometriosis cases significantly had shorter AGDAF, 22.9 ± 2.6 mm, compared with the control group, 27.3 ± 3.5 mm (P < 0.001). Lower FASL and higher BCL2 expression were associated with endometriosis (P < 0.001). The combined measurement of AGDAF (cut-off point 24.55 mm) with FASL and BCL2 was associated with endometriosis (P < 0.001). The combined diagnostic sensitivity, specificity, positive predictive value, and negative predictive value of AGDAF, FASL, and BCL2 were 83%, 78%, 87.3%, and 69.6%, respectively. The area under the curve was greater for AGDAF, FASL, and BCL2 in combination than for individual measurements. CONCLUSION: Combining short AGDAF with high BCL2 and low FASL is a highly sensitive, non-invasive diagnostic tool for endometriosis.

(R,R)-BD-AcAc2 Mitigates Chronic Colitis in Rats: A Promising Multi-Pronged Approach Modulating Inflammasome Activity, Autophagy, and Pyroptosis.

Ulcerative colitis is a chronic and incurable form of inflammatory bowel disease that can increase the risk of colitis-associated cancer and mortality. Limited treatment options are available for this condition, and the existing ones often come with non-tolerable adverse effects. This study is the first to examine the potential benefits of consuming (R,R)-BD-AcAc2, a type of ketone ester (KE), and intermittent fasting in treating chronic colitis induced by dextran sodium sulfate (DSS) in rats. We selected both protocols to enhance the levels of ß-hydroxybutyrate, mimicking a state of nutritional ketosis and early ketosis, respectively. Our findings revealed that only the former protocol, consuming the KE, improved disease activity and the macroscopic and microscopic features of the colon while reducing inflammation scores. Additionally, the KE counteracted the DSS-induced decrease in the percentage of weight change, reduced the colonic weight-to-length ratio, and increased the survival rate of DSS-insulted rats. KE also showed potential antioxidant activities and improved the gut microbiome composition. Moreover, consuming KE increased the levels of tight junction proteins that protect against leaky gut and exhibited anti-inflammatory properties by reducing proinflammatory cytokine production. These effects were attributed to inhibiting NFκB and NLRP3 inflammasome activation and restraining pyroptosis and apoptosis while enhancing autophagy as revealed by reduced p62 and increased BECN1. Furthermore, the KE may have a positive impact on maintaining a healthy microbiome. To conclude, the potential clinical implications of our findings are promising, as (R,R)-BD-AcAc2 has a greater safety profile and can be easily translated to human subjects.

Ganetespib (STA-9090) augments sorafenib efficacy via necroptosis induction in hepatocellular carcinoma: Implications from preclinical data for a novel therapeutic approach.

Sorafenib, a multikinase inhibitor, is a first-line treatment for advanced hepatocellular carcinoma, but its long-term effectiveness is limited by the emergence of resistance mechanisms. One such mechanism is the reduction of microvessel density and intratumoral hypoxia caused by prolonged sorafenib treatment. Our research has demonstrated that HSP90 plays a critical role in conferring resistance to sorafenib in HepG2 cells under hypoxic conditions and N-Nitrosodiethylamine-exposed mice as well. This occurs through the inhibition of necroptosis on the one hand and the stabilization of HIF-1α on the other hand. To augment the effects of sorafenib, we investigated the use of ganetespib, an HSP90 inhibitor. We found that ganetespib activated necroptosis and destabilized HIF-1α under hypoxia, thus enhancing the effectiveness of sorafenib. Additionally, we discovered that LAMP2 aids in the degradation of MLKL, which is the mediator of necroptosis, through the chaperone-mediated autophagy pathway. Interestingly, we observed a significant negative correlation between LAMP2 and MLKL. These effects resulted in a reduction in the number of surface nodules and liver index, indicating a regression in tumor production rates in mice with HCC. Furthermore, AFP levels decreased. Combining ganetespib with sorafenib showed a synergistic cytotoxic effect and resulted in the accumulation of p62 and inhibition of macroautophagy. These findings suggest that the combined therapy of ganetespib and sorafenib may offer a promising approach for the treatment of hepatocellular carcinoma by activating necroptosis, inhibiting macroautophagy, and exhibiting a potential antiangiogenic effect. Overall, continued research is critical to establish the full therapeutic potential of this combination therapy.

Primary hyperparathyroidism associated with colorectal cancer: case report.

The association between colorectal cancer and primary hyperparathyroidism has been reported as case reports in the literature. There are few data regarding the molecular explanation of such coexistence. Here we report a case with synchronous pathologies of primary hyperparathyroidism and colorectal cancer. Furthermore, the patient has a positive family history of the same two pathologies in one of his first-degree relatives. We reviewed the literature to clarify and explain the relationship between these two diseases. We aimed to shed light on the coexistence of such conditions and to clarify if there is a relation between them or if it is just a coincidence.

One Anastomosis Gastric Bypass (OAGB) with a 150-cm Biliopancreatic Limb (BPL) Versus a 200-cm BPL, a Systematic Review and Meta-analysis.

This is a systematic review and meta-analysis that assessed the impact of performing OAGB with a 150-cm BPL versus a 200-cm BPL concerning weight loss, comorbidities remission, and adverse nutritional effects. The analysis included studies that compared patients who underwent OAGB with a 150-cm BPL and 200-cm BPL. Eight studies were eligible for this review after searching in the EMBASE, PubMed central database, and Google scholar. The pooled analysis revealed favoring the 200-cm BPL limb length for weight loss, with a highly significant difference in the TWL% (p=0.009). Both groups showed comparable comorbidities remission. Significantly higher ferritin and folate deficiency rates were found in the 200-cm BPL group. Considering a 200-cm BPL when performing OAGB delivers a better weight loss outcome than a 150-cm BPL, which is at the expense of a more severe nutritional deficiency. No significant differences were found regarding the comorbidities' remission.

Bisphenol A enhances apoptosis, fibrosis, and biochemical fluctuations in the liver of adult male rats with possible regression after recovery.

Bisphenol A (BPA) is an environmental contaminant that might be harmful. Human exposure to BPA can occur during the fetal and postnatal periods and extends throughout life. This study aimed to estimate the effects of oral administration of BPA on rat liver and assess the possibility of recovery after cessation. Adult male albino rats were orally administered with BPA (50 mg/kg body weight) for 8 weeks, and then one group was left to recover for 4 weeks. Histological, immunohistochemical, biochemical, and quantitative real-time polymerase chain reaction assessments were performed. Loss of hepatic architecture, vascular dilatation congestion, and exudation, as well as cellular vacuolation, fat accumulation, and pyknotic nuclei were detected. Furthermore, inflammatory infiltration, localized metaplasia, and excessive collagen deposition in the portal triad were observed. Expression of Bcl-2-associated X protein and transforming growth factor beta 1 was prominent, denoting apoptosis and fibrosis. After the administration of BPA, serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, cholesterol, triglycerides, and low-density lipoproteins were enhanced. Additionally, total protein, albumin, and high-density lipoproteins decreased. After a recovery for 4 weeks, hepatic cellular and vascular pathologies returned to normal, except for some inflammatory infiltration. Regarding biochemical affection, most of the parameters were directed toward normal during recovery. However, most of them were still significantly different from controls. This explored BPA hepatotoxicity from structural and functional aspects, and the possible spontaneous reversibility was confirmed. However, the precise mechanisms underlying hepatotoxicity or recovery need more in-depth investigations.

Percutaneous needle aspiration versus catheter drainage in the management of liver abscess: an updated systematic review and meta-analysis.

BACKGROUND: Liver abscesses differ in their aetiology, location, and number. Image-guided percutaneous drainage techniques are the currently used management for liver abscesses. We conducted our study to compare the clinical safety and efficacy of percutaneous needle aspiration (PNA) to percutaneous catheter drainage (PCD). METHODS: A systematic review of major reference databases was undertaken in February 2022 for randomized controlled trials (RCTs) that compare PNA to PCD in treating liver abscess patients. The quality of the included trials was assessed using the Cochrane tool. Statistical meta-analysis was conducted using RevMan and open meta-analyst software. RESULTS: Fifteen RCTs were included in this review, with 1676 patients enrolled. The overall quality of the included trials was moderate, with most domains of unclear risk. PCD was superior to PNA in the success rate (RR = 1.23; 95% CI [1.12, 1.36], P < 0.00001), time for achieving 50% reduction of cavity size (MD = -2.32; 95% CI [-3.07, -1.57], P < 0.00001), and time for clinical improvement (MD = -1.92; 95% CI [-2.55, -1.28], P < 0.00001). The two modalities did not differ in the days of hospital stay, duration of IV antibiotics, and time needed for total or subtotal reduction of cavity size (P = 0.36, P = 0.06 and P = 0.40, respectively). High heterogeneity levels were detected. Regarding major complications, the two modalities were equally safe (P = 0.39). CONCLUSION: PCD has a higher success rate and results in a faster 50% reduction in the abscess cavity size and clinical improvement. The two modalities are equally safe.

Right Ventricular Outflow Tract Intimal Sarcoma Extending into the Main Pulmonary Artery: A Case Report.

Intimal sarcomas are rare malignant mesenchymal tumors that arise in the large arteries and rarely in the heart. Herein, we report the case of a 55-year-old man who was referred for further assessment of a right ventricular outflow tract mass. Assessment with cardiac magnetic resonance imaging revealed an enhancing mobile mass arising within the right ventricular outflow tract and extending into the main pulmonary artery. The initial diagnostic possibilities included thrombus and myxoma. The patient underwent surgical recession of the mass and the histopathology examination confirmed the diagnosis of cardiac intimal sarcoma.

Targeting Hydrogen Sulfide Modulates Dexamethasone-Induced Muscle Atrophy and Microvascular Rarefaction, through Inhibition of NOX4 and Induction of MGF, M2 Macrophages and Endothelial Progenitors.

Long-term use of Glucocorticoids produces skeletal muscle atrophy and microvascular rarefaction. Hydrogen sulfide (H2S) has a potential role in skeletal muscle regeneration. However, the mechanisms still need to be elucidated. This is the first study to explore the effect of Sodium hydrosulfide (NaHS) H2S donor, against Dexamethasone (Dex)-induced soleus muscle atrophy and microvascular rarefaction and on muscle endothelial progenitors and M2 macrophages. Rats received either; saline, Dex (0.6 mg/Kg/day), Dex + NaHS (5 mg/Kg/day), or Dex + Aminooxyacetic acid (AOAA), a blocker of H2S (10 mg/Kg/day) for two weeks. The soleus muscle was examined for contractile properties. mRNA expression for Myostatin, Mechano-growth factor (MGF) and NADPH oxidase (NOX4), HE staining, and immunohistochemical staining for caspase-3, CD34 (Endothelial progenitor marker), vascular endothelial growth factor (VEGF), CD31 (endothelial marker), and CD163 (M2 macrophage marker) was performed. NaHS could improve the contractile properties and decrease oxidative stress, muscle atrophy, and the expression of NOX4, caspase-3, Myostatin, VEGF, and CD31 and could increase the capillary density and expression of MGF with a significant increase in expression of CD34 and CD163 as compared to Dex group. However, AOAA worsened the studied parameters. Therefore, H2S can be a promising target to attenuate muscle atrophy and microvascular rarefaction.

Cystinosis in Pediatric Renal Transplant Recipients: A Case-Control Study From Kuwait.

OBJECTIVES: Cystinosis is the most frequent cause of the inherited renal Fanconi syndrome and is also potentially treatable. In this study, we have reported our single-center experience of the longterm outcomes of kidney transplant in patients with cystinosis. MATERIALS AND METHODS: Pediatric patients with cystinosis (n = 17) were compared with a matched control group without cystinosis (n = 126). The 2 groups were compared with regard to demographic data, posttransplant complications, and graft and patient outcomes. RESULTS: Most patients with cystinosis were male teenagers (52.9%) with comparable mean age (12.4 ± 4.1 vs 14 ± 3.1 years) versus the group without cystinosis. The 2 study groups were comparable with regard to type of dialysis, type of donor, blood group, and pretransplant comorbidities (P > .05). Patients with cystinosis received significantly more potent induction therapy (P < 0.05), but both groups were maintained on comparable immunosuppressive regimens (mostly tacrolimus based) (P > .05). Most grafts in both groups displayed immediate graft function. The percentage of patients with cystinosis with primary graft function was significantly higher than the percentage of those patients without cystinosis who had primary graft function (P = .024); this was associated with a relatively lower baseline creatinine level, although this was not significant (P > .05). Posttransplant complications, especially posttransplant diabetes, cytomegalovirus viremia, or BK nephropathy, were comparable (P > .05). Moreover, patient and graft survival rates were similar in the 2 groups (P > .05). CONCLUSIONS: Under standard immunosuppression, renal transplant and cysteamine therapy were safe with good long-term outcomes in patients with cystinosis. Studies that can include more patients and that have longer follow-up are needed to better understand the nature of this genetic disease and to discover the best treatment options.

Prognostic Implications of MALAT1 and BACH1 Expression and Their Correlation with CTCs and Mo-MDSCs in Triple Negative Breast Cancer and Surgical Management Options.

BACKGROUND: Triple negative breast cancer (TNBC) is a biologically separate entity of breast cancer that cannot get benefits from targeted or endocrine therapy. OBJECTIVE: To assess the expression of MALAT1 and BACH1, as well as monocyte-myeloid-derived suppressor cell (Mo-MDSC) levels and circulating tumor cell (CTC) count in TNBC to correlate these markers with the clinic-pathological criteria of TNCB patients and to evaluate their roles as predictive markers for selection of the patients that can be operated by oncoplastic conserving breast surgery. METHODS: Eighty-eight TNBC were managed by modified doughnut breast oncoplastic surgery in early stages and by modified radical mastectomy for patients with late stages unsuitable for breast-conserving. All were examined for MALAT1 and BACH1 expression by immunohistochemistry and RT-PCR as well as Mo-MDSC levels and CTCs. RESULTS: MALAT1 and BACH1 expressions are correlated with the larger size, lymph node, distance metastasis, and TNM staging (p < 0.05). CTCs ≥ 5 and high MO-MDSCs were significantly more in TNBC with MALAT1 and BACH1 overexpression. The survival study proved that DFS for patients with both positive expression of MALAT1 and BACH1 was shorter than that of one positive expression, and both negative expression p ≤ 0.001, CTCs ≥ 5, and high Mo-MDSCs are associated with poor outcomes. No significant difference between modified round block and modified radical mastectomy techniques as regards recurrence. However, all postoperative management outcomes were significantly better in patients operated by oncoplastic conserving breast surgery. CONCLUSION: BACH1 and MALAT1 expressions are significantly upregulated in TNBC. They are correlated with CTCs and Mo-MDCs, and all are associated with poor outcomes. Not all TNBC patients have a bad prognosis, patients negative for one of MALAT1 and BACH1 or both, have a slightly good prognosis, and so can be managed by breast oncoplastic conserving surgery.

Identification of naphthyridine and quinoline derivatives as potential Nsp16-Nsp10 inhibitors: a pharmacoinformatics study.

This research is a recent effort to explore some new heterocyclic compounds as novel and potential nonstructural protein-16-nonstructural protein-10 (Nsp16-Nsp10) inhibitors for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inhibition. The SARS-CoV-2 is causative agent of coronavirus disease 2019 (COVID-19) pandemic. A set of 58 molecules belongs to the naphthyridine and quinoline derivatives have been recently synthesized and considered for structure-based virtual screening against Nsp16-Nsp10. Molecular docking was virtually performed to screen for anti-SARS-CoV-2 activity against Nsp16-Nsp10. Fourteen out of fifty-eight compounds were exhibited binding affinity higher than co-crystal bound ligand s-adenosylmethionine (SAM) toward Nsp16-Nsp10. Further, the in silico pharmacokinetics assessment was carried out and it was found that two molecules possess the acceptable pharmacokinetic profile, hence considered promising Nsp16-Nsp10 inhibitors. The binding interaction analysis was revealed some crucial binding interactions between the final selected two molecules and ligand-binding amino acid residues of Nsp16-Nsp10 protein. In order to explore the characteristics of the protein-ligand complex and how selected small molecules retained inside the receptor cavity in dynamic states, all-atoms conventional molecular dynamics (MD) simulation was performed. Several factors were obtained from the MD simulation trajectory evidently suggested the potentiality of the molecules and stability of the protein-ligand complex. Finally, the binding affinity of both molecules and SAM was explored through the MM-GBSA approach which explained that both molecules possess strong affection towards the Nsp16-Nsp10. Hence, from the pharmacoinformatics assessment, it can be concluded that both heterocyclic compounds might be crucial for SARS-CoV-2 inhibition, subjected to experimental validation.Communicated by Ramaswamy H. Sarma.

Eicosapentaenoic and docosahexaenoic acids attenuate methotrexate-induced apoptosis and suppression of splenic T, B-Lymphocytes and macrophages with modulation of expression of CD3, CD20 and CD68.

Methotrexate (MTX) is a chemotherapeutic agent used for cancer and autoimmune disorders. MTX may cause multi-organ affections. However, few studies examined MTX-induced splenic suppression and therapeutic modalities against it. This is the first study to explore the efficacy of omega-3 fatty acids; Eicosapentaenoic (EPA) and Docosahexaenoic (DHA) against MTX-induced splenic suppression and its effect on splenic macrophages and lymphocytes. Five groups of Sprague Dawley rats were used. Group 1 received saline; group 2: omega-3 only; group 3: a single dose of MTX (20 mg/kg); groups 4 and 5: MTX (20 mg/kg) + either omega-3 (150) or (300 mg/kg) once daily, respectively, given for two days before MTX and three days after it. Splenic tissues were then removed, evaluated for oxidative stress markers; GSH, MDA, and for mRNA expression of the apoptotic marker caspase-3, the anti-apoptotic marker Bcl-2 and the inflammatory cytokine TNFα. Moreover, H&E stain, Prussian blue stain for iron, and immunohistochemical staining for TNFα, T lymphocyte marker; CD3, B lymphocyte marker; CD20, and macrophage marker; CD68, were performed with morphometric analysis. EPA and DHA could decrease the MTX-induced increase in the histopathological injury score, splenic hemosiderin, splenic MDA, mRNA expression of TNFα, caspase-3 and could increase the MTX-induced decrease in Splenic GSH and mRNA expression for Bcl-2. It also decreased the MTX-induced elevation in the immunopositive area of TNFα, and increased the area percentage of CD3+, CD20+ and CD68+ cells. Therefore, omega-3 can be a promising adjuvant to help MTX action with prevention of its deleterious effects on spleen.

Investigating the Effect of Repeated High Water Pressure on the Compressive and Bond Strength of Concrete with/without Steel Bar.

The application of reinforced concrete for permanent and temporary deep ocean structures has recently become more prevalent; however, the static and dynamic effects of high water pressure on concrete remain unexplored. This paper investigates the influence of high water pressure (60 MPa) on four series of concrete cylinders with and without an embedded steel bar under sustained and cyclic loading conditions. The residual compressive strength, bond strength, and associated evolution of surface and internal damage are evaluated after exposing concrete cylinders to a water pressure of 60 MPa. The first series is exposed to sustained water pressure for 7 and 60 days, while the other series is tested under repeated water pressure for 10, 20, 30, 60, and 150 cycles. The results reveal that residual compressive strength falls immediately by 16% within 7 days of sustained high water pressure, but the strength then remains stable up to 60 days. Under repeated high water pressure, residual compressive strength gradually reduces by up to 40% until 60 cycles, after which it remains reasonably stable until 150 cycles as crack propagation is arrested at a certain depth within the concrete cylinders. The bond strength between the steel bar and matrix is observed to decrease considerably under repeated cycles of 60 MPa water pressure up to 26%. The damage gradually propagates at the matrix/steel bar interface under the repeated water pressure, resulting in a reduction in residual pullout capacity.

Anticoagulantes, Antiplaquetarios y sus implicaciones en cirugía: una revisión de la literatura / Anticoagulants, Anti-platelets, and their implications in Surgery: A Literature review

All health care providers should be aware of the impact of bleeding disorders on their patients during any surgical procedures. The knowledge of the mechanisms of hemostasis and optimized management are very important. Initial recognition of a bleeding disorder, in such patients with a systemic pathologic process, may occur in surgical practice. The surgical treatment of those patients might be complicated during the surgery due to the use of anticoagulant and/or antiplatelet medications raises a challenge in the daily practice of surgical professionals. Adequate hemostasis is critical for the success of any surgical procedure because bleeding problems can give rise to complications associated with important morbidity-mortality. Besides, prophylactic, restorative, and surgical care of patients with any bleeding disorders is handled skillfully by practitioners who are well educated regarding the pathology, complications which could arise, and surgical options associated with these conditions. The purpose of this paper is to review common bleeding disorders and their effects on the surgical aspect. Many authors consider that patient medication indicated for the treatment of background disease should not be altered or suspended unless so indicated by the prescribing physician. Local hemostatic measures have been shown to suffice for controlling possible bleeding problems resulting from surgery.

Efficacy and safety of amlodipine/valsartan/hydrochlorothiazide single pill combination in Egyptian patients with hypertension uncontrolled on any dual therapy: an observational study.

Objective: Hypertension is a serious health problem in Egypt, with prevalence rate of 17% as reported in 2015. Despite receiving treatment, many do not achieve blood pressure (BP) control. The current study aimed to evaluate the efficacy and tolerability of amlodipine/valsartan/hydrochlorothiazide (Aml/Val/HCTZ) single pill combination (SPC) in patients with hypertension from Egypt, who were uncontrolled on any dual therapy.Methods: In this prospective, open label, multicenter, 12-week observational, cohort study, two doses of Aml/Val/HCTZ (5/160/12.5 mg or 10/160/25 mg) SPC were used to evaluate mean change in BP after 12 weeks (primary endpoint). Safety assessments included presence and intensity of ankle edema and other adverse events (AEs).Results: Data were collected from 1080 patients who were treated according to the routine medical practice across 47 centers in Egypt. Significant reduction in systolic and diastolic BP (SBP/DBP) was observed from 165.5 ± 12.83/100.8 ± 7.03 mmHg at baseline to 129.7 ± 8.35/80.6 ± 5.25 mmHg after 12 weeks of treatment (p < .0001). Majority of patients (76.85%) reached the BP goal of <140/90 mmHg. The most commonly reported AE was ankle edema (10.92%).Conclusions: Aml/Val/HCT SPC significantly reduced BP and was well tolerated in Egyptian patients with hypertension not controlled on any previous dual therapy.

Edaravone attenuates lung injury in a hind limb ischemia-reperfusion rat model: A histological, immunohistochemical and biochemical study.

Edaravone is a potent free radical scavenger that has a promising role in combating many acute lung injuries. Ischemia/reperfusion process is a serious condition that may lead to multiple organ dysfunctions. This work was designed to investigate novel mechanisms underlying ischemia/reperfusion-induced lung injury and to evaluate the protective role of edaravone. Thirty adult male rats were divided into three experimental groups; operated with no ischemia (Sham-group), ischemia/reperfusion (I/R) group and edaravone-I/R group. Hind limb ischemia was carried out by clamping the femoral artery. After two hours of ischemia for the hind limb, the rat underwent 24h of reperfusion. Rats in the edaravone-I/R group received edaravone (3mg/kg), 30min before induction of ischemia. At the end of the I/R trial, specimens from the lungs were processed for histological, immunohistochemical, enzyme assay, and RT-qPCR studies. Specimens from I/R group showed focal disruption of the alveolar architecture. Extensive mononuclear cellular infiltration particularly with neutrophils and dilated congested blood capillaries were observed. A significant increase in iNOS, NF-κB, and COX-2 immunoreaction was detected and confirmed by RT-qPCR. Ultrastructural examination showed RBCs and fluid inside alveoli, cellular infiltration, and vacuolations of the inter-alveolar septum. In addition to the presence of extravasated neutrophils and RBCs within the inter-alveolar septum. In contrast, minimal changes were observed in rats which received edaravone before the onset of the ischemia. It could be concluded that edaravone exerted a potent protective effect against lung injury induced by a hind limb I/R in rats through its antioxidant and anti-inflammatory activities.

Width-to-length ratio comparison between ameloblastomas and odontogenic keratocysts in the body of the mandible: A preliminary study.

PURPOSE: The purpose of this study was to investigate the utility of the width-to-length ratio for the differentiation of ameloblastomas and odontogenic keratocysts in the body of the mandible. MATERIALS AND METHODS: This study retrospectively reviewed 9 patients with ameloblastomas and 9 patients with odontogenic keratocysts using cone-beam computed tomography. The width-to-length ratio was determined by measuring the ratio between the greatest buccolingual dimension and the greatest perpendicular anteroposterior dimension of the lesion on the axial view. One-way analysis of variance was used to examine the difference in the width-to-length ratio between the 2 types of lesions. Statistical significance was tested at P<0.05. RESULTS: Ameloblastomas showed a mean width-to-length ratio of 0.64, whereas odontogenic keratocysts showed a mean width-to-length ratio of 0.41. The cut-off value with which the 2 types of lesions were differentiated was 0.5. The width-to-length ratios of ameloblastomas were significantly higher than those of odontogenic keratocysts (P<0.05). CONCLUSION: The width-to-length ratio might be used to differentiate between ameloblastomas and odontogenic keratocysts.