Mohammad Alqudah

Broadly Neutralizing Antibodies: An Approach to Control HIV-1 Infection

ABSTRACT Although available antiretroviral therapy (ART) has changed human immunodeficiency virus (HIV)-1 infection to a non-fatal chronic disease, the economic burden of lifelong therapy, severe adverse ART effects, daily ART adherence, and emergence of ART-resistant HIV-1 mutants require prospecting for alternative therapeutic modalities. Indeed, a growing body of evidence suggests that broadly neutralizing anti-HIV-1 antibodies (BNAbs) may offer one such feasible alternative. To evaluate their therapeutic potential in established HIV-1 infection, we sought to address recent advances in pre-clinical and clinical investigations in this area of HIV-1 research. In addition, we addressed the obstacles that may impede the success of such immunotherapeutic approach, suggested strategic solutions, and briefly compared this approach with the currently used ART to open new insights for potential future passive immunotherapy for HIV-1 infection.

Osteoblastoma is a metabolically active benign bone tumor on 18F-FDG PET imaging.

We describe a case of a 9-y-old girl who on 18F-FDG PET imaging was found to have a highly metabolically active sacral tumor with an average standarized uptake value of 6.2. The tumor was proven to be osteoblastoma by pathologic examination. Osteoblastoma is a relatively rare benign primary bone tumor and occurs predominantly in patients younger than 20 y. The most common area of involvement is the spine. Osteoblastoma has been reported to be metabolically active on 18F-FDG PET imaging, with an average standarized uptake value of 3.2, which renders 18F-FDG PET imaging unable to differentiate benign from malignant primary bone tumors. To our knowledge, only 5 cases of osteoblastoma evaluated by 18F-FDG PET imaging have been reported in the literature; all were metabolically active on 18F-FDG PET imaging. The objective of this case report is to show that a metabolically active primary bone tumor on 18F-FDG PET imaging might be benign and not necessarily malignant.

Mechanisms and regulation of neurotrophin synthesis and secretion.

Neurotrophins are secreted proteins that are synthesized as pre-pro-neurotrophins on the rough endoplasmic reticulum, which are subsequently processed and then secreted as mature proteins. During synthesis, neurotrophins are sorted in the trans-Golgi apparatus into 2 pathways of secretion; the constitutive and the regulated pathways. Neurotrophins in the constitutive pathway are secreted cautiously without any trigger, while in the regulated pathway of secretion an external stimulus elevates the calcium concentration intracellularly leading to neurotrophin release. The regulation of sorting and secretion of neurotrophins is critical for several processes in the body, such as synaptic plasticity, neurodegenerative disorders, demyelination disease, and inflammation. The purpose of this review is to summarize the current mechanisms of neurotrophin sorting and secretion.

Association of brain-derived neurotrophic factor and interleukin-6 serum levels with depressive and anxiety symptoms in hemodialysis patients

OBJECTIVE This study assessed the possible association of serum brain-derived neurotrophic factor (BDNF) and interleukin-6 (IL-6) with depressive and anxiety symptoms in hemodialysis (HD) patients. METHOD An analytical cross-sectional study was conducted over 274 HD patients from March to October 2017. The Hospital Anxiety and Depression Scale (HADS) was utilized to evaluate depressive (HADS-D) and anxiety (HADS-A) symptoms. The HADS-D/A is a self-report instrument that has a maximum score of 21. Serum BDNF and IL-6 were measured using enzyme-linked immunosorbant assay (ELISA). RESULTS Serum IL-6 was significantly higher in patients with depressive symptoms compared to normal (20.47 ± 4.27 pg/mL for HADS-D ≥11 versus 9.26 ± 1.59 pg/mL for HADS-D <7, p = 0.014). Multivariable regression analysis revealed that IL-6, education level, hypertension, and dialysis duration were significant predictors of HADS-D. Also, gender, education level, hypertension, and the number of dialysis sessions/week were significant predictors of HADS-A. Significant positive correlation was shown between HADS-D and IL-6 (r = 0.1729, p = 0.004). CONCLUSION Collectively, HD patients with depressive symptoms showed higher levels of IL-6, supporting previous findings that the circulating inflammatory mediator IL-6 can be used as a biomarker for prediction of depressive symptoms in HD patients. Further longitudinal or interventional studies are needed to further validate this association.

Phenelzine reduces the oxidative damage induced by peroxynitrite in plasma lipids and proteins

Abstract Peroxynitrite is a reactive nitrogen species produced in the intravascular compartment from superoxide anion and nitric oxide. Peroxynitrite destroys blood plasma proteins and membranes of red blood cells and of platelets. This explains why excessive production of peroxynitrite contributes to diseases and to ageing. Therapeutics that antagonize peroxynitrite may delay ageing and the progression of disease. We developed an in vitro assay that allows the investigation of the oxidative damage caused by peroxynitrite in the intravascular compartment. This assay correlates the damage with the rate of formation of protein carbonyl groups, 3-nitrotyrosine (3-NT) and thiobarbituric acid reactive substances. Using this assay, we evaluated the ability of phenelzine, a scavenger of reactive aldehydes, to antagonize the effects of peroxynitrite. Herein, we showed that phenelzine significantly decreased the lipid peroxidative damage caused by peroxynitirite in blood plasma and platelets. Moreover, it inhibited carbonyl group and 3-NT formation in blood plasma and platelet proteins.

Prostate cancer in Jordanian-Arab population: ERG status and relationship with clinicopathologic characteristics

TMPRSS2/ERG fusion was found to be the most common genetic event in prostate adenocarcinoma. There is a strong correlation between the fusion and ERG-positive immunostaining. Many studies showed racial variation in ERG expression in prostate cancer patients. There is no data however on the rate of ERG-positive cancer in Jordanian or Arab population. We evaluated the frequency and the significance of ERG fusion in Jordanian-Arab population using immunohistochemistry for ERG. The cohort included 193 prostate cancer specimens: 109 needle core biopsies, 45 radical prostatectomies, 37 transurethral resections of prostate, and 2 enucleation specimens. We found ERG reactivity in 64 (33.2%) of evaluated cases. The observed ERG frequency in the Jordanian-Arab population is lower than the one documented in North America, but it is higher than in Asian patient cohorts. The ERG positivity was significantly associated with lower baseline prostate-specific antigen but was unrelated to patient age, Gleason Score, or the novel Gleason Grade Groups. In the 45 prostatectomy cases, ERG did not correlate with the pathologic stage, margin, nodal status, and the biochemical recurrence, and it did not appear to represent an important prognosticator.

A high weekly dose of cholecalciferol and calcium supplement enhances weight loss and improves health biomarkers in obese women

Obesity, a chronic condition associated with several life-threatening diseases, affects a significant proportion of the global population and has long been associated with vitamin D deficiency. The prevalence of both obesity and vitamin D deficiency has increased dramatically in Jordan in recent decades, especially among women. Few studies in Jordan and the surrounding area address this issue. In this study, we hypothesize that calcium and vitamin D have beneficial effects on weight reduction and metabolic profile in obese women. The objective of this study is to examine the effect of vitamin D3 and calcium supplementation on anthropometric measurements and some blood metabolites. Forty-five obese female subjects with vitamin D deficiency were recruited by a dietitian and randomly assigned to the same weight loss diet in addition to the following treatments (4 groups): control (CON), no prescribed supplements; vitamin D3 (Diet/D), given a high weekly dose of cholecalciferol (50 000 IU/subject/week); calcium (Diet/Ca), given 1200 mg/dL calcium/subject/day; vitamin D3 plus Ca (Diet/Ca/D), given cholecalciferol (50 000 IU/subject/week) and calcium (1200 mg/dL calcium/subject/day). Results revealed that after 3 months of supplementation, the Diet/Ca/D group subjects experienced a significant reduction (P ≤ .05) in weight (10.49 kg), BMI (4.61 ± 2 kg/m2), waist circumference (11.41 ± 8.9 cm), body fat percentage (2.43 ± 1.7%), FBG (25.81 ± 11.4 mg/dL), PTH (27.58 ± 8.9 pg/mL), cholesterol (0.56 ± 0.2 mmol/L), and triglycerides (0.53 ± 0.21 mmol/L) when compared to the Diet/Ca and the CON groups. Interestingly, however, the CON group showed a significant increase in serum PTH concentration (9.51 ± 3.8 pg/mL, P ≤ .05). Based on these results, a combined Ca and vitamin D3 supplement appears to enhance weight loss and improve some of the blood metabolic profiles in obese women subjected to a weight loss diet, thus supporting our study hypothesis.

Clinical and Demographic Features of Basal Cell Carcinoma in North Jordan

Basal cell carcinoma (BCC) is the most common cancer affecting humans. It almost has no tendency for metastasis; however it can be destructive to surrounding tissue. Patients with darker skin colors have lower risk of developing skin cancers and the clinical characteristics may differ from populations with lighter skin colors. Methods. This is a retrospective clinical study (2003–2017). Data on age, gender, and location of tumor were collected and analyzed. Results. 335 cases were identified. Males tend to get BCC at a younger age than females. Face was the most common site in both males and females. Cheeks and nose were the most likely areas of the face to be involved. Scalp was the most common extrafacial site to be involved in males; however in females scalp was much less likely to be involved. Conclusion. BCC is less common in populations with darker skin. Males were more affected and at an earlier age compared to females. Facial skin followed by scalp was the most common site affected. Skin phototype, cultural and religious dress type, and different sun exposure behavior may explain many of the clinical and demographic findings related to BCC in patients with darker skin tones.

Glucagon-like peptide-1 exerts anti-inflammatory effects on mouse colon smooth muscle cells through the cyclic adenosine monophosphate/nuclear factor-κB pathway in vitro

Background Intestinal smooth muscle cells (SMCs) undergo substantial morphological, phenotypic, and contractile changes during inflammatory bowel disease (IBD). SMCs act as a source and target for different inflammatory mediators, however their role in IBD pathogenesis is usually overlooked. Glucagon-like peptide-1 (GLP-1) is an incretin hormone reported to exert multiple anti-inflammatory effects in different tissues including the gastrointestinal tract through various mechanisms. Aim The aim of this research is to explore the effect of GLP-1 analog exendin-4 on the expression and secretion of inflammatory markers from mouse colon smooth muscle cells (CSMCs) after stimulation with lipopolysaccharide (LPS). Materials and methods Freshly isolated CSMCs from male BALB/c mice were cultured in DMEM and treated with vehicle, LPS (1 μg/mL), LPS+exendin-4 (50 nM), or LPS+exendin-4 (100 nM) for 24 h. Expression of inflammatory cytokines was then evaluated by antibody array membrane. Results CSMCs showed basal expression of several cytokines which was enhanced with the induction of inflammation by LPS. However, exendin-4 (50 and 100 nM) significantly (p<0.05) reduced the expression of multiple cytokines including tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α), T cell activation gene-3 (TCA-3), stromal cell-derived factor-1 (SDF-1), and macrophage colony stimulating factor (M-CSF). To confirm these results, expression of these cytokines was further assessed by enzyme-linked immunosorbent assay and real-time polymerase chain reaction and similar results were also observed. Moreover, secretion of TNF-α and IL1-α into the conditioned media was significantly downregulated by exendin-4 when compared to LPS-treated cells. Furthermore, LPS increased NF-κB phosphorylation, while exendin-4 significantly reduced levels of NF-κB phosphorylation. Conclusion These data indicate that GLP-1 analogs can exert significant anti-inflammatory effects on CSMCs and can potentially be used as an adjunct treatment for inflammatory bowel conditions.

Vitamin C prevents memory impairment induced by waterpipe smoke: role of oxidative stress.

Abstract Waterpipe tobacco smoking (WTS) was previously shown to be associated with memory deficits, which were related to oxidative stress. Vitamin C (VitC) has established antioxidant properties against memory deficits associated with several diseases and conditions. In this study, the potential protective effect of VitC on memory impairment induced by WTS exposure was evaluated in a rat model. VitC was administered to animals via oral gavage (100 mg/kg/day, 6 days a week for 4 weeks). At the same period, animals were exposed to WTS for one hour/day, 6 days a week for 4 weeks. Using radial arm water maze (RAWM), behavioral tests were conducted to evaluate the spatial learning and memory. In addition, hippocampal levels of oxidative stress biomarkers were analyzed. WTS exposure impaired both short- and long-term memory (p < .05). On the other hand, VitC protected memory impairment induced by WTS (p < .05). Moreover, VitC prevented the reduction in hippocampus ratio of GSH/GSSG (p < .05) induced by WTS. Furthermore, WTS reduced hippocampus activity of glutathione peroxidase (GPx) and catalase, which were also normalized by VitC treatment. However, thiobarbituric acid reactive substance (TBARS) levels were not changed by WTS and/or by VitC (p > .05). In conclusion, WTS resulted in inducing memory impairment, which was prevented by VitC administration. This could be related to preserving hippocampus antioxidant mechanisms by VitC during WTS exposure.