Subcutaneous immunoglobulins (SCIG) for chronic inflammatory demyelinating polyneuropathy (CIDP): A comprehensive systematic review of clinical studies and meta-analysis.

BACKGROUND: Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) presents significant treatment challenges due to its chronic nature, varied clinical presentations, and rarity. Subcutaneous immunoglobulin (SCIG) has emerged as a maintenance therapy, offering potential advantages in administration and patient experience over the previously recognized intravenous immunoglobulin (IVIG). METHODS: We included all clinical studies involving CIDP patients treated with SCIG from eleven databases up to March 2024. RESULTS: 50 clinical studies were included in the systematic review, with 22 involved in the meta-analysis. These studies offer clinical data on around 1400 CIDP patients. Almost all studies considered SCIG a maintenance therapy, with the majority of results suggesting it as a viable substitute that may offer comparable or enhanced advantages. Studies covered aspects such as efficacy, safety, quality of life, practicality, economic evaluation, and patient preference. Meta-analysis showed SCIG significantly improved muscle strength and sensory function, had fewer and milder side effects, reduced relapse rates, and received a strong preference. CONCLUSIONS: Findings suggest that SCIG for CIDP maintenance not only provides a more feasible alternative, with economic evaluations showing considerable cost reductions over time, and patient preference for SCIG being pronounced, but may also deliver comparable or superior health outcomes. Ongoing research lines on formulations, techniques, and direct comparative studies are critical to further illuminate, enhance, and expand SCIG's role in treatment.

Green potentiometric electrode for determination of salbutamol in biological samples.

Clinical drug analyses and identification of pharmaceuticals in biological samples are highly crucial for therapeutic drug monitoring, pharmacokinetic studies, and screening of illicit drugs. Various analytical tools, such as potentiometric electrodes, are used to conduct these investigations. These potentiometric electrodes are superior to other techniques in terms of greenness and cost efficacy, and thus present a good alternative for researchers. In this study, we develop an advanced electrode for the in-situ monitoring of salbutamol in plasma, this electrode was synthesized using multiwalled carbon nanotubes (MWCNT) as hydrophobic conductive substance and copper oxide nanoparticle (CuO NP) as a surface modifier, the developed electrode was compared to traditional liquid contact electrode as well as solid contact electrode and proved its superiority. The use of MWCNT improved the stability of the electrode via preventing the formation of this water layer and the CuO NP improved the sensitivity due to its high surface area and rich electronic properties. CuO NP modified electrode was used for the determination of salbutamol with a Nernstian slope of 57.4 over a linearity range of range 1.0 × 10-7- 1.0 × 10-2 M, and a detection limit of 4.0 × 10-7 M. The proposed electrode was effectively applied for the determination of the cited drug in rat plasma without interference and compared with chromatographic reported method. The proposed method is economic as it has a low sample analysis cost, time saving and needs fewer manipulation steps and a simple convenient device. It also proved to be a greener method when compared with chromatographic methods using an eco-scale metric system.

Performance Analysis of Dual-Hop Hybrid RF-UOWC NOMA Systems.

The hybrid combination between underwater optical wireless communication (UOWC) and radio frequency (RF) is a vital demand for enabling communication through the air-water boundary. On the other hand, non-orthogonal multiple access (NOMA) is a key technology for enhancing system performance in terms of spectral efficiency. In this paper, we propose a downlink NOMA-based dual-hop hybrid RF-UOWC with decode and forward (DF) relaying. The UOWC channels are characterized by exponential-generalized Gamma (EGG) fading, while the RF channel is characterized by Rayleigh fading. Exact closed-form expressions of outage probabilities and approximated closed-form expressions of ergodic capacities are derived, for each NOMA individual user and the overall system as well, under the practical assumption of imperfect successive interference cancellation (SIC). These expressions are then verified via Monte-Carlo simulation for various underwater scenarios. To gain more insight into the system performance, we analyzed the asymptotic outage probabilities and the diversity order. Moreover, we formulated and solved a power allocation optimization problem to obtain an outage-optimal performance. For the sake of comparison and to highlight the achievable gain, the system performance is compared against a benchmark orthogonal multiple access (OMA)-based system.

A wavelet-based deep learning pipeline for efficient COVID-19 diagnosis via CT slices.

The quick diagnosis of the novel coronavirus (COVID-19) disease is vital to prevent its propagation and improve therapeutic outcomes. Computed tomography (CT) is believed to be an effective tool for diagnosing COVID-19, however, the CT scan contains hundreds of slices that are complex to be analyzed and could cause delays in diagnosis. Artificial intelligence (AI) especially deep learning (DL), could facilitate and speed up COVID-19 diagnosis from such scans. Several studies employed DL approaches based on 2D CT images from a single view, nevertheless, 3D multiview CT slices demonstrated an excellent ability to enhance the efficiency of COVID-19 diagnosis. The majority of DL-based studies utilized the spatial information of the original CT images to train their models, though, using spectral-temporal information could improve the detection of COVID-19. This article proposes a DL-based pipeline called CoviWavNet for the automatic diagnosis of COVID-19. CoviWavNet uses a 3D multiview dataset called OMNIAHCOV. Initially, it analyzes the CT slices using multilevel discrete wavelet decomposition (DWT) and then uses the heatmaps of the approximation levels to train three ResNet CNN models. These ResNets use the spectral-temporal information of such images to perform classification. Subsequently, it investigates whether the combination of spatial information with spectral-temporal information could improve the diagnostic accuracy of COVID-19. For this purpose, it extracts deep spectral-temporal features from such ResNets using transfer learning and integrates them with deep spatial features extracted from the same ResNets trained with the original CT slices. Then, it utilizes a feature selection step to reduce the dimension of such integrated features and use them as inputs to three support vector machine (SVM) classifiers. To further validate the performance of CoviWavNet, a publicly available benchmark dataset called SARS-COV-2-CT-Scan is employed. The results of CoviWavNet have demonstrated that using the spectral-temporal information of the DWT heatmap images to train the ResNets is superior to utilizing the spatial information of the original CT images. Furthermore, integrating deep spectral-temporal features with deep spatial features has enhanced the classification accuracy of the three SVM classifiers reaching a final accuracy of 99.33% and 99.7% for the OMNIAHCOV and SARS-COV-2-CT-Scan datasets respectively. These accuracies verify the outstanding performance of CoviWavNet compared to other related studies. Thus, CoviWavNet can help radiologists in the rapid and accurate diagnosis of COVID-19 diagnosis.

Exendin-4 Attenuates Remodeling in the Remote Myocardium of Rats After an Acute Myocardial Infarction by Activating ß-Arrestin-2, Protein Phosphatase 2A, and Glycogen Synthase Kinase-3 and Inhibiting ß-Catenin.

PURPOSE: This study tested if the protective anti-remodeling effect of GLP-1 agonist Exendin-4 after an acute myocardial infarction (MI) in rats involves inhibition of the Wnt1/ß-catenin signaling pathway. METHODS: Rats were divided into sham, sham + Exendin-4 (10 µg/day, i.p), MI, and MI + Exendin-4. MI was introduced to rats by permanent left anterior descending coronary artery (LAD) ligation. RESULTS: On day 7 post-infraction, MI rats showed LV dysfunction with higher serum levels of cardiac markers. Their remote myocardia showed increased mRNA and protein levels of collagen I/III with higher levels of reactive oxygen species (ROS) and inflammatory cytokines, as well as protein levels of Wnt1, phospho-Akt, transforming growth factor (TGF-ß1), Smad, phospho-Smad3, α-SMA, caspase-3, and Bax. They also showed higher protein levels of phospho-glycogen synthase kinase-3ß (p-GSK3ß), as well as total, phosphorylated, and nuclear ß-catenin with a concomitant decrease in the levels of cyclic adenosine monophosphate (cAMP), mRNA of manganese superoxide dismutase (MnSOD), and protein levels of Bcl-2, ß-arrestin-2, and protein phosphatase-2 (PP2A). Administration of Exendin-4 to MI rats reduced the infarct size and reversed the aforementioned signaling molecules without altering protein levels of TGF-1ß and Wnt1 or Akt activation. Interestingly, Exendin-4 increased mRNA levels of MnSOD, protein levels of ß-arrestin-2 and PP2A, and ß-catenin phosphorylation but reduced the phosphorylation of GSK3ß and Smad3, and total ß-catenin levels in the LV of control rats. CONCLUSION: Exendin-4 inhibits the remodeling in the remote myocardium of rats following acute MI by attenuating ß-catenin activation and activating ß-arrestin-2, PP2A, and GSK3ß. Graphical Abstract A graphical abstract that illustrates the mechanisms by which Exendin-4 inhibits cardiac remodeling in remote myocardium of left ventricle MI-induced rats. Mechanisms are assumed to occur in the cardiomyocytes and/or other resident cells such as fibroblast. Β-catenin activation and nuclear translocation are associated with increased synthesis of inflammatory cytokines and transforming growth factor ß-1 (TGF-ß1). GSK3ß is inhibited by phosphorylation at Ser9. Under normal conditions, ß-catenin is degraded in the cytoplasm by the active GSK3ß-dependent degradation complex (un-phosphorylated) which usually phosphorylates ß-catenin at Ser33/37/Thr41. After MI, TGF-ß1, and Wnt 1 levels are significantly increased, the overproduction of Wnt1 induces ß-catenin stabilization and nuclear translocation through increasing the phosphorylation of disheveled (DVL) protein which in turn phosphorylates and inhibits GSK3ß. TGF-ß1 stimulates the phosphorylation of Smad-3 and subsequent nuclear translocation to activate the transcription of collage 1/III and α-smooth muscle actin (α-SMA). Besides, TGF-ß1 stabilizes cytoplasmic ß-catenin levels indirectly by phosphorylation of Akt at Thr308-induced inhibition of GSK3ß by increasing phosphorylation of Ser9. Exendin-4, and possibly through G protein-coupled receptors (GPCRs), increases levels of cAMP and upregulates ß-arrestin-2 levels. Both can result in a positive inotropic effect. Besides, ß-arrestin-2 can stimulate PP2A to dephosphorylation Smad3 (inhibition) and GSK3ß (activation), thus reduces fibrosis and prevents the activation of ß-catenin and collagen deposition.

Grape seed extract protects against amiodarone - induced nephrotoxicity and ultrastructural alterations associated with the inhibition of biomarkers of inflammation and oxidative stress in rats.

Amiodarone (AMD) is one of the highly effective antiarrhythmic agents used for treating refractory arrhythmias. It is well known to have long-term administration side effects such as nephrotoxicity. The possible ameliorative effects of antioxidant grape seed extract; on the extent of tissue damage in AMD-induced nephrotoxicity has not been investigated before. Twenty-four albino rats were used in this study and divided into four groups (n = 6). The 1st group served as an untreated control group, under the same laboratory conditions, the 2nd group received (100 mg/kg/day) of grape seed extract (GSE), the 3rd group, AMD-treated group, received AMD (40 mg/kg/day) and the 4th group received both AMD and GSE in the same doses as the previous groups. AMD-treated group showed abnormal glomerular capillaries with wrinkling basement membranes damaged mesangial cells and distorted proximal tubules with plenty of lysosomes. Ultrastructural alterations were also observed in this group. This was also associated with a significant increase in biomarkers of kidney injury (creatinine), oxidative stress ((Decreased SOD and increased MDA) and biomarkers of inflammation IL-6) in comparison to the control group. Supplementation of GSE to AMD group for eight weeks counteracted these effects. It caused an improvement in histological and t ultrastructure changes of the renal tissues associated with decreased creatinine and biomarkers of oxidative stress and inflammation in comparison to AMD-treated group. We conclude that GSE protects against AMD-induced kidney injuries in rats, which is associated with the inhibition of biomarkers of inflammation and oxidative stress.

Comparison between Malerba osteotomy and combined Evans/medial displacement calcaneal osteotomies for the management of flexible pes planus in young adults: a prospective randomised control trial, three years follow-up.

PURPOSE: The aim of the current study is to evaluate the functional and radiological outcomes of Malerba osteotomy in comparison to the standardized combined Evans/Medial Displacement Calcaneal Osteotomy (MDCO) in the management of symptomatic flexible pes planus in young adults. METHODS: Prospective randomized control trial included 34 feet (33 patients), 17 cases in each group. Functionally, patients were assessed by AOFAS and FADI scores. Radiographic evaluation included calcaneal pitch, lateral talo-1st metatarsal, AP talo-first metatarsal, AP talo-calcaneal angles, and the talar coverage percentage. RESULTS: Pre-operative and three years follow-up scores and angles were compared between both groups. No statistically significant difference could be detected between both groups (P value 0.87). However, the data showed statistically significant difference in each group when comparing (pre-operative and third year follow-up scores and angles) (P value < 0.001). The mean union rate was eight weeks in Malerba group and nine weeks in Evans/MDCO group. No incidence of nonunion. Complications like calcaneocuboid subluxation, calcaneal anterior process fracture, and lateral column pain were exclusively reported in Evans/MDCO group. CONCLUSION: Malerba osteotomy is a strong valid option for the operative management of flexible pes planus in young adults. Authors recommend Malerba osteotomy in all mild and moderate deformities due to lower complication rate while the combined Evans/MDCO is preferred in severe deformity due to relatively higher corrective power with consideration of possible complications.

Exendin-4 protects the hearts of rats from ischaemia/reperfusion injury by boosting antioxidant levels and inhibition of JNK/p66 Shc/NADPH axis.

Exendin-4, a glucagon-like peptide-1 receptor agonist, was shown to protect against cardiac ischaemia/reperfusion (I/R) injury by suppressing oxidative stress. p66 Shc, a pro-oxidant and an apoptotic protein, is activated in the infarcted left ventricles (LVs) after induction of I/R. This study investigated if the cardiac protective effect of Exendin-4 against I/R injury in rats involves inhibition of p66 Shc and to determine the underlying mechanisms behind this. Adult male rats (n = 12/group) were divided into four groups as a sham, a sham + Exendin-4, an I/R, and an I/R + Exendin-4. Exendin-4 was administered to rats 7 days before the induction of I/R. Ischaemia was induced by ligating the left anterior descending (LAD) coronary artery for 40 minutes followed by reperfusion for 10 minutes. The infarct myocardium was used for further analysis. Exendin-4 significantly reduced infarct area (by 62%), preserved LV function and lowered serum levels of LDH and CK-MB in I/R-induced rats. Also, it significantly reduced LV levels of ROS and MDA and protein levels of cytochrome-c and cleaved caspase-3 but significantly increased levels of glutathione (GSH) and manganese superoxide dismutase (MnSOD) in LVs of I/R rats indicating antioxidant and anti-apoptotic effects. Furthermore, it inhibited JNK and p66 Shc activation and downregulated protein levels of p66 Shc and NADPH oxidase with no effect on protein levels/activity of p53 and PKCßII. Of note, Exendin-4 also increased GSH and MnSOD in LVs of control rats. In conclusion, Exendin-4 cardioprotective effect in I/R hearts is mediated mainly by antioxidant effect and inhibition of JNK/P66 Shc/NADPH oxidase.

Light and transmission electron microscopy of the haptoral sclerites of the monogenean gill parasite Macrogyrodactylus clarii.

The present study represents the first detailed description of the haptoral sclerites of Macrogyrodactylus clarii Gussev 1961. Light microscopy reveals outgrowths of the hamuli roots; two lateral spine-like extensions of the hood-like accessory sclerites; a ridged, fan-shaped distal end of an accessory sclerite; and two thread-like accessory sclerites with biforked ends associated with the pointed hooked region of each hamulus. Transmission electron microscopy (TEM) reveals the presence of parallel tubules in the root of the hamuli and structural differences along the length of the hamulus including the root, shaft, and pointed hooked region. The root consists of two layers, the shaft four layers and pointed hooked region only one layer with dense outer serrations. Characteristic features of the hamulus root are the presence of longitudinally orientated parallel tubules in its central core and parallel electron-dense ridges in the outer layer of its middle region; features not observed in either the shaft or the pointed hooked region. Each hamulus blade of M. clarii is associated with haptoral gland cells producing electron-dense secretory bodies. The 16 marginal hooklets each consist of a blade (sickle) articulating with a handle at the guard region and a domus. TEM revealed structural differences between the handle, the blade at the articulation region, and the distal hooked region. The domus, a filamentous thread-like sclerite at the light microscope level, consists of two electron-dense, fibrous thickenings connected to each other by a cytoplasmic process. Each marginal hooklet is associated with a small cavity and a large reservoir of homogeneous particles and secretory bodies. The possible functions of these structures are discussed in relation to equivalent features in other monogeneans.

What constitutes the fat signal detected by MRI in the spine of patients with ankylosing spondylitis? A prospective study based on biopsies obtained during planned spinal osteotomy to correct hyperkyphosis or spinal stenosis.

OBJECTIVE: Study the MRI signal of fatty lesions (FL) by immunohistological analysis of vertebral body biopsies of patients with ankylosing spondylitis (AS) compared with degenerative disc disease (DDD). METHODS: Biopsies obtained during planned surgery from vertebral edges where MRI signals of FL was detected were stained with H&E. Immunofluorescence (IF) staining was performed to quantify osteoblasts and osteoclasts. Bone marrow (BM) composition, grade of cellularity and quantification of cells were analysed on six randomly chosen high-power fields (HPF; 0.125 mm2) at 200-fold magnification per patient by two experienced researchers in a blinded manner. RESULTS: Biopsies of 21 patients with AS and 18 with DDD were analysed. Adipocytes were found in the BM of 19 patients with AS (90.5%) versus 5 with DDD (27.8%) (p<0.001), while inflammatory infiltrates were found in in the BM of 8 patients with AS (38.1%) versus 14 with DDD (77.8%) (p=0.035) and fibrosis in 6 patients with AS (28.6%) versus 4 with DDD (22.2%) (p=n .s.). The most frequently detected cells were adipocytes in AS (43.3%) versus DDD (16.1%, p=0.002) and inflammatory mononuclear cells in DDD (55%) versus AS (11.0%, p=0.001). Using IF staining, there was more osteoblastic than osteoclastic activity (6.9 vs 0.17 cells/HPF) in FL as compared with inflammatory BM (1.3 vs 7.4 cells/HPF), respectively. CONCLUSION: MRI FL correspond to presence of adipocytes, resulting to change of cellular homeostasis towards diminution of osteoclasts in the BM of patients with AS. The cross-talk between the different cell types and osteitis, fat and new bone formation needs further study.

Efficacy of Injectable and Immersion Polyvalent Vaccine against Streptococcal Infections in Broodstock and Offspring of Nile tilapia (Oreochromis niloticus).

A vaccine against streptococcosis, lactococcosis and enterococcosis in tilapia was formulated, ME-VAC Aqua Strept, as a polyvalent inactivated vaccine containing Streptococcus agalactiae, S. iniae, Lactococcus garvieae and Enterococcus faecalis along with a nano-particulate adjuvant. Use of ME-VAC Aqua Strept by injection or immersion resulted in an improved non-specific and adaptive immunity of broodstock and offspring. Intra-peritoneal vaccination of tilapia broodstock increased the total leukocyte count, phagocytosis, lysozyme activity, antibody titer, number of seeds/vaccinated broodstock, seeds quality and survival rates. Also, immersion mass vaccination of tilapia larvae provided a long period of protection up to three months, with a relative percent of survivability (RPS) not less than 60% at this time. To our knowledge, this vaccine may be the first to offer a combined protection against streptococcosis, lactococcosis and enterococcosis in tilapia. The results support the use of this vaccine as an effective tool for disease control and well-being of fish.

Chronic consumption of a high-fat diet rich in corn oil activates intrinsic cell death pathway and induces several ultrastructural changes in the atria of healthy and type 1 diabetic rat.

This study investigates the effect of chronic consumption of a high-fat diet rich in corn oil (CO-HFD) on atrial cells ultrastructure, antioxidant levels and markers of intrinsic cell death of both control and type 1 diabetes mellitus (T1DM)-induced rats. Adult male rats (10 rats/group) were divided into four groups: control fed standard diet (STD) (3.82 kcal/g, 9.4% fat), CO-HFD (5.4 kcal/g, 40% fat), T1DM fed STD, and T1DM + CO-HFD. CO-HFD and T1DM alone or in combination impaired systolic and diastolic functions of rats and significantly reduced levels of GSH and the activity of SOD, enhanced lipid peroxidation, increased protein levels of P53, Bax, cleaved caspase-3, and ANF and decreased levels of Bcl-2 in their atria. Concomitantly, atrial cells exhibited fragmentation of the myofibrils, disorganized mitochondria, decreased number of atrionatriuretic factor (ANF) granules, and loss of gap junctions accompanied by changes in capillary walls. Among all treatments, the severity of all these findings was more severe in T1DM and most profound in the atria of T1DM + CO-HFD. In conclusion, chronic consumption of CO-HFD by T1DM-induced rats elicits significant biochemical and ultrastructural damage to rat atrial cells accompanied by elevated oxidative stress and mitochondria-mediated cell death.

Development of simultaneous quantification method of loteprednol etabonate (LE) and its acidic metabolites, and analysis of LE metabolism in rat.

Loteprednol etabonate (LE) is a soft corticosteroid with two labile ester bonds at 17α- and 17ß-positions. Its corticosteroidal activity disappears upon hydrolysis of either ester bond. Hydrolysis of both ester bonds produces the inactive metabolite, Δ1-cortienic acid (Δ1-CA). The simple high-performance liquid chromatography method using acetic acid gradient was developed for the simultaneous determination of LE and its acidic metabolites. LE was hydrolyzed in rat plasma with a half-life of 9 min. However, LE hydrolysis was undetectable in rat liver and intestine. LE hydrolysis in rat plasma was completely inhibited by paraoxon and bis(p-nitrophenyl) phosphate, thus identifying carboxylesterase as the LE hydrolase. Rat plasma carboxylesterase had a Km of 6.7 µM for LE. In contrast to the disappearance rate of LE in rat plasma, the formation rate of 17α-monoester and Δ1-CA was markedly low, and a main hydrolysate of LE was not detected in rat plasma. The metabolism of LE proceeded via different pathways in human and rat plasma. LE was slowly hydrolyzed by paraoxonase in human plasma to 17α-monoester with a half-life of 12 h, but by carboxylesterase in rat plasma to yield undetectable products, presumed to include the unstable 17ß-monoester.

Environmental factors controlling potentially toxic element behaviour in urban soils, El Tebbin, Egypt.

This study focuses on the assessment of surface soils from industrially polluted region (El Tebbin) of southern Cairo, Egypt. The impact of agricultural, residential and industrial land use on soils developed from Nile river sediments has significantly compromised their function. Previous evidence has shown that the food chain is contaminated and enhances risk of contaminant exposure of the residential communities. This study investigates factors controlling potentially toxic element (PTE) distribution (Co, Ni, Pb, Cd, Zn, Cr and Cu) in El Tebbin soils and provide estimates of their mobility and bioavailability. The PTE concentrations are characterised by high variability as result of the variety of natural and anthropogenic influences. Highest spatial variability is found for Zn, Cd, Pb and Cu (C.V = 260.0%, 280.4%, 140.8% and 159.6% respectively) and enrichment factors indicate strong anthropogenic inputs. For Co and Ni, relatively low spatial variability (C.V = 65.8% and 45.0% respectively) with depletion in Ni suggests a relatively minor contribution from anthropogenic sources. For Cr, a more uniform distribution pattern showing depletion to minimal enrichment across the study area (C.V = 19.2%) reflects almost exclusive lithogenic control. Using principle component analysis (PCA) to explore concentration data reveals that the major inputs affecting PTE distribution are modified by primary soil properties (texture and pH). Their relative bioavailability (identified through sequential chemical extraction) relates strongly to local input sources. Those elements dominated by lithogenic input (Ni and Co) were found predominantly in soil residual fractions (95.6% and 90.5% respectively), while elements with stronger anthropogenic contributions (Cd, Zn, Pb and Cu) showed much higher portion in the more mobile and bioavailable fractions obtained from sequential chemical extraction, with average proportions of the totals being 62.6%, 57%, 40.7% and 39.2% respectively. Those PTEs with strong anthropogenic influence are potentially much more mobile for bioaccumulation in food chain with increased health risk for exposed residents and are confirmed by elevated concentrations of Cd, Zn, Pb and Cu recorded in local plant species. The main pollution sources were further highlighted by cluster analysis and showed vehicle traffic and specific industrial activities but which varied significantly from site to site. The identification of sources through the approach developed here allows prioritisation of monitoring and regulatory decisions by the local government to reduce further environmental exposure of the local population.

Cardioprotective effect of ghrelin against myocardial infarction-induced left ventricular injury via inhibition of SOCS3 and activation of JAK2/STAT3 signaling.

The molecular mechanisms through which ghrelin exerts its cardioprotective effects during cardiac remodeling post-myocardial infarction (MI) are poorly understood. The aim of this study was to investigate whether the cardioprotection mechanisms are mediated by modulation of JAK/STAT signaling and what triggers this modulation. Rats were divided into six groups (n = 12/group): control, sham, sham + ghrelin (100 µg/kg, s.c., daily, starting 1 day post-MI), MI, MI+ ghrelin, and MI+ ghrelin+ AG490, a potent JAK2 inhibitor (5 mg/kg, i.p., daily). All treatments were administered for 3 weeks. Administration of ghrelin to MI rats improved left ventricle (LV) architecture and restored cardiac contraction. In remote non-infarcted areas of MI rats, ghrelin reduced cardiac inflammation and lipid peroxidation and enhanced antioxidant enzymatic activity. In addition, independent of the growth factor/insulin growth factor-1 (GF/IGF-1) axis, ghrelin significantly increased the phosphorylation of JAK2 and Tyr702 and Ser727 residues of STAT3 and inhibited the phosphorylation of JAK1 and Tyr701 and Ser727 residues of STAT1, simultaneously increasing the expression of BCL-2 and decreasing in the expression of BAX, cleaved CASP3, and FAS. This effect coincided with decreased expression of SOCS3. All these beneficial effects of ghrelin, except its inhibitory action on IL-6 expression, were partially and significantly abolished by the co-administration of AG490. In conclusion, the cardioprotective effect of ghrelin against MI-induced LV injury is exerted via activation of JAK2/STAT3 signaling and inhibition of STAT1 signaling. These effects were independent of the GF/IGF-1 axis and could be partially mediated via inhibition of cardiac IL-6.

EFFICACY AND FREQUENCY OF INTRAVITREAL AFLIBERCEPT VERSUS BEVACIZUMAB FOR MACULAR EDEMA SECONDARY TO CENTRAL RETINAL VEIN OCCLUSION.

PURPOSE: To compare the safety, efficacy, and frequency of intravitreal injection of aflibercept and bevacizumab for treatment of macular edema secondary to central retinal vein occlusion. DESIGN: Prospective, comparative, randomized, interventional study. PATIENTS AND METHODS: Eyes with macular edema secondary to central retinal vein occlusion were randomized between two groups according to the intravitreal injection used. Group A included eyes treated with intravitreal aflibercept, and Group B included eyes treated with intravitreal bevacizumab injections. The inclusion criteria were macular edema secondary to central retinal vein occlusion and follow-up duration of at least 12 months after the first injection. Exclusion criteria were macular ischemia, associated diabetes, hypertensive or renal retinopathy, other retinal disease, and previous anti-vascular endothelial growth factor injection. The main outcome measures are central foveal thickness, best-corrected visual acuity, time intervals between injections, improved retinal nonperfusion, and any reported complication. RESULTS: Group A included 39 patients with a mean age of 57.4 ± 8.2 years. Group B included 40 eyes with a mean age of 56.5 ± 9.1 years. Twelve months after the first injection, central foveal thickness significantly improved from 475.45 ± 71.05 m to 259.11 ± 20.67 m in Group A and from 460.22 ± 89.38 m to 264.29 ± 32.05 m in Group B; best-corrected visual acuity significantly improved from 0.81 ± 0.16 logarithm of the minimum angle of resolution (20/125) to 0.34 ± 0.14 logarithm of the minimum angle of resolution (20/40) in Group A and from 0.73 ± 0.15 logarithm of the minimum angle of resolution (20/100) to 0.33 ± 0.17 logarithm of the minimum angle of resolution (20/40) in Group B; the mean number of injections was 3.72 ± 2.93 in Group A and was 5.44 ± 2.85 in Group B (P < 0.05); and the mean interval between injections was 54.23 ± 8.47 days in Group A and was 35.12 ± 7.76 days in Group B (P < 0.05). Retinal nonperfusion improved in 9/12 eyes in Group A and in 3/8 eyes in Group B (P < 0.05). CONCLUSION: Both aflibercept and bevacizumab are comparably effective for treatment of macular edema secondary to central retinal vein occlusion without significant complications. However, the burden of frequent intravitreal injections could be significantly reduced when using aflibercept.

Acylated ghrelin protects aorta damage post-MI via activation of eNOS and inhibition of angiotensin-converting enzyme induced activation of NAD(P)H-dependent oxidase.

NAD(P)H dependent oxidase derived-reactive oxygen species (ROS) due to activation of the renin-angiotensin-aldosterone system (RAAS) in blood vessels postmyocardial infarction MI or during the HF leads to endothelium dysfunction and enhanced apoptosis. Acylated ghrelin (AG) is a well-reported cardioprotective and antiapoptotic agent for the heart. AG receptors are widely distributed in most of blood vessels, suggesting a role in the regulation of endothelial function and survival. This study investigated if AG can protect aorta of rats' postmyocardial infarction (MI)-induced damage and endothelial dysfunction. Adult male rats were divided into four groups of (1) Sham, (2) Sham + AG, (3) MI, and (4) MI + AG. Vehicle (normal saline) or AG (100 µ/kg) was administered to rats for 21 consecutive days, after which, numerous biochemical markers were detected by blot. Both histological and electron microscope studies were carried on aortic samples from MI-induced rats. AG increased protein levels of both total and phosphorylated forms of endothelial nitric oxide synthase (eNOS and p-eNOS, respectively). Only in MI-treated rats, AG prevented the decreases in the levels of reduced glutathione (GSH) and superoxide dismutase (SOD) and lowered levels of malondialdehyde (MDA) and glutathione disulfide (GSSG). Concomitantly, it lowered the increased protein levels of angiotensin-converting enzyme (ACE), p22phox and cleaved caspase-3 and prevented the aorta histological and ultrustructural abnormalities induced by MI.

Conjunctival Autograft Combined With Either Preoperative Mitomycin C Injection or Intraoperative Local Mitomycin C Over the Medial Rectus Muscle Tendon in Primary Pterygium Surgery.

PURPOSE: To evaluate and compare the recurrence rate and complications of conjunctival autograft (CAG) combined with preoperative mitomycin C (MMC) injection versus CAG with intraoperative local MMC over the medial rectus muscle tendon in primary pterygium. STUDY DESIGN: Randomized prospective study. METHODS: This study included 108 eyes of 108 patients with primary fleshy or growing pterygium. All patients were from rural areas and less than 50 years old. Fifty-three patients were treated with injection of 0.1 mL of 0.15 mg/mL MMC into the body of pterygium followed 1 day later by pterygium excision and CAG (group I), and 55 patients were treated with pterygium excision and local application of 0.2 mg/mL MMC for 2 min over the medial rectus tendon followed by CAG (group II). The minimum follow-up period was 18 months. RESULTS: Two patients from group I and one patient from group II did not complete the follow-up period and were excluded. There were no statistically significant differences between the two groups regarding age, sex, laterality, or follow-up period. Recurrence occurred in 2 eyes in group I (3.92%) and 1 eye in group II (1.85%); (P=0.52). All recurrences occurred in male patients of less than 30 years of age. No significant complications were encountered in both groups. CONCLUSIONS: Both preoperative MMC injection followed 1 day later by pterygium excision with CAG, and pterygium excision and intraoperative local application of MMC on the medial rectus tendon are successful in treating primary pterygium with low recurrence rate and few complications.

Determination of virulence and antibiotic resistance pattern of biofilm producing Listeria species isolated from retail raw milk.

BACKGROUND: One of the foodborne pathogens is Listeria monocytogenes, which causes serious invasive illness in elderly and immunocompromised patients, pregnant women, newborns and infants ranking second after salmonellosis because of its high case fatality rate. Listerial cow mastitis marked by abnormal milk, increased cell counts and reduced production has not been reported. Therefore, apparently healthy cows can be reservoirs of L. monocytogenes. A number of 203 udder milk samples from apparently healthy animals (buffalo, n = 100; cow, n = 103) were collected and tested for Listeria. Isolated colonies on the PALCAM agar were Listeria species confirmed according to their biochemical and the Christie-Atkins-Munch-Petersen (CAMP) reactions. The Listeria species pathogenicity of was tested by phosphatidylinositol-specific phospholipase C, DL-alanine-ß-naphthylamide HCl, Dalanine-p-nitroanilide tests, chick embryo, mice inoculation tests, Vero cell cytotoxicity and biofilm formation. The virulence-associated genes, hlyA, plcB, actA and iap associated with Listeria were molecularly assayed. RESULTS: The 17 isolated Listeria spp. represented a prevalence rate of 8.4 %. Of these 3 (1.4 %), 2 (1 %), 5 (2.5 %), 4 (2 %) and 3 (1.5 %) were confirmed as L. monocytogenes, L. innocua, L. welshimeri, L. seelegeri, respectively. While the L. monocytogenes isolate displayed all the four virulence-associated genes, L. seelegeri carried the hlyA gene only. The L. monocytogenes had a strong in vitro affinity to form a biofilm, in particular serotype 4 which is associated with human infections. L. monocytogenes showed resistance for 9/27 antibiotics. CONCLUSIONS: The biofilm forming capability of the Listeria spps. makes them particularly successful in colonizing surfaces within the host thus being responsible for persistence infections and due to their antimicrobial resistant phenotype that this structure confers. In addition, strains belonging to serotypes associated with human infections and characterized by pathogenic potential (serotype 4) are capable to persist within the processing plants forming biofilm and thus being a medical hazard.

Synthesis and molecular modeling of antimicrobial active fluoroquinolone-pyrazine conjugates with amino acid linkers.

Novel fluoroquinolone-pyrazine conjugates 7a-h with amino acid linkers were synthesized in good yields utilizing benzotriazole chemistry. Antimicrobial bioassay showed that the synthesized bis-conjugates have antimicrobial properties comparable to the parent drugs. Compound 7h showed superior antibacterial activity against Staphylococcus aureus and Streptococcus pyogenes (MIC=74.6 µM and 149.3 µM, respectively). This matched well with the estimated values obtained from 3D-pharmacophore and 2D-QSAR studies (MIC=67 µM and 92.9 µM, respectively).