Repurposed anti-cancer epidermal growth factor receptor inhibitors: mechanisms of neuroprotective effects in Alzheimer’s disease

Numerous molecular mechanisms are being examined in an attempt to discover disease-modifying drugs to slow down the underlying neurodegeneration in Alzheimer’s disease.Recent studies have shown the beneficial effects of epidermal growth factor receptor inhibitors on the enhancement of behavioral and pathological sequelae in Alzheimer’s disease.Despite the promising effects of epidermal growth factor receptor inhibitors in Alzheimer’s disease,there is no irrefutable neuroprotective evidence in well-established animal models using epidermal growth factor receptor inhibitors due to many un-explored downstream signaling pathways.This caused controversy about the potential involvement of epidermal growth factor receptor inhibitors in any prospective clinical trial.In this review,the mystery beyond the under-investigation of epidermal growth factor receptor in Alzheimer’s disease will be discussed.Furthermore,their molecular mechanisms in neurodegeneration will be explained.Also,we will shed light on SARS-COVID-19 induced neurological manifestations mediated by epidermal growth factor modulation.Finally,we will discuss future perspectives and under-examined epidermal growth factor receptor downstream signaling pathways that warrant more exploration.We conclude that epidermal growth factor receptor inhibitors are novel effective therapeutic approaches that require further research in attempts to be repositioned in the delay of Alzheimer’s disease progression.     

The effect of early vs. delayed postpartum insertion of the LNG-IUS on breastfeeding continuation: a systematic review and meta-analysis of randomised controlled trials

Abstract

Objective: The aim of the study was to compare early vs. delayed postpartum insertion of the 52?mg levonorgestrel intrauterine system (LNG-IUS).

Methods: The databases of PubMed, Scopus, Web of Science and CENTRAL were searched to February 2019. The search comprised randomised controlled trials (RCTs) comparing early vs. delayed postpartum insertion of the LNG-IUS. Data were extracted and combined in a meta-analysis. Pooled results were expressed as the relative risk (RR) with 95% confidence interval (CI). The main outcome measures were breastfeeding continuation, LNG-IUS expulsion, uterine perforation, LNG-IUS use, satisfaction and number of pregnancies.

Results: Twelve RCTs were included, comprising 1006 women in total. Our analysis indicated no significant difference between early and delayed insertion of the LNG-IUS in terms of any breastfeeding continuation (RR 0.99; 95% CI 0.84, 1.16; p?=?0.88). After removal of heterogeneity, there was a statistically significant superiority in LNG-IUS use at the endpoint in the early insertion group compared with the delayed insertion group (RR 1.27; 95% CI 1.07, 1.51; p?=?0.006). LNG-IUS expulsion was significantly less in the delayed insertion group in comparison with the early insertion group (RR 5.32; 95% CI 2.68, 10.53; p?=?0.00001). No significant differences were found between the groups in satisfaction, number of pregnancies and risk of uterine perforation.

Conclusion: Early postpartum insertion of the LNG-IUS has no negative effects on breastfeeding continuation. Early postpartum insertion may be used as an alternative to delayed postpartum insertion.     

Treatment of Melasma with Intralesional Tranexamic Acid Versus Cryotherapy

Background Melasma is a relatively common, acquired facial skin disorder of hyperpigmentation. Though it occurs in both sexes, nearly 90% of patients are female. It manifests as hyperpigmented macules and patches distributed symmetrically on the face, neck, and, rarely, the upper limbs. OBJECTIVE: The aim of this study was to evaluate and compare the clinical efficacy and adverse effects of intralesional injection of tranexamic acid (TA) versus cryotherapy in the treatment of melasma.MethodsPatients were divided into two groups: Group A and Group B. Group A comprised 28 patients aged 27 to 50 years. They received localized intralesional injections of TA. According to Wood’s light examination, patients were divided into two subtypes; 13 patients with mainly dermal-type melasma and 15 patients with mainly mixed-type melasma. Family history was obtained in 12 patients. Group B comprised 28 patients aged 29 to 46 years were included. They were treated with cryotherapy. According to Wood’s light examination, the patients were divided into two subtypes of melasma; 8 patients with mainly dermal-type melasma and 10 patients with mainly mixed-type melasma.ResultsThere were no statistically significant differences between Group A and Group B according to contraception, sun exposure, and family history. There was a statistically significant difference between Group A and Group B according to previous treatment. There was no statistically significant difference between the two groups according to drug allergy. There were no statistically significant differences according to systemic disease or general examination.ConclusionIntralesional tranexamic acid is a safe and effective method for the treatment of melasma with no risk of PIH, thrombosis, or bleeding; however, more sessions with longer follow-up periods are recommended, as the final response may take several months to occur. Cryotherapy was neither safe nor effective due to the risk of PIH.     

Knowledge of the effects of indoor air quality on health among women in Jordan.

OBJECTIVE: To assess the extent of knowledge about symptoms relating to respiratory illnesses and home environments among a random sample of 200 urban Jordanian women. METHOD: This customized, validated, cross-sectional questionnaire evaluated the knowledge of these women about the association between the indoor environment and health, the presence or absence of indoor discomforts, symptoms of respiratory illnesses, and behaviors related to the home environment such as cleaning practices. RESULTS: Results showed an alarming rate of smoking in the homes; the extent of knowledge was moderate but higher among those exhibiting symptoms and those with children. Cleaning practices associated with healthy home environments were reported at a high rate but seemed to be based on cultural influences. CONCLUSIONS: This type of information is crucial to the formation of health education programs and policy recommendations for pollutant source and exposure reductions in homes in the Middle East and other developing countries.     

Collagen induced MMP-2 activation in human breast cancer

Summary Matrix metalloproteinase-2 (MMP-2), a zymogen requiring proteolytic activation for catalytic activity, has been implicated broadly in the invasion and metastasis of many cancer model systems, including human breast cancer (HBC). MMP-2 has been immunolocalized to carcinomatous human breast, where the degree of activation of MMP-2 correlates well with tumor grade and patient prognosis. Using Matrigel assays, we have stratified HBC cell lines for invasivenessin vitro, and compared this to their potential for metastatic spread in nude mice. HBC cell lines expressing the mesenchymal marker protein vimentin were found to be highly invasivein vitro, and tended to form metastases in nude mice. We have further discovered that culture on collagen-I gels (Vitrogen^TM; Vg) induces MMP-2-activator in highly invasive but not poorly invasive HBC cell lines. As seen for other MMP-2-activator inducing regimens, this induction requires protein synthesis and an intact MMP-2 hemopexin-like domain, appears to be mediated by a cell surface activity, and can be inhibited by metalloproteinase inhibitors. The induction is highly specific to collagen I, and is not seen with thin coatings of collagen I, collagen IV, laminin, or fibronectin, or with 3-dimensional gels of laminin, Matrigel, or gelatin. This review focuses on collagen I and MMP-2, their localization and source in HBC, and their relationship(s) to MMP-2 activation and HBC metastasis. The relevance of collagen I in activation of MMP-2in vivo is discussed in terms of stromal cell: tumor cell interaction for collagen I deposition, MMP-2 production, and MMP-2-activation. Such cooperativity may existin vivo for MMP-2 participation in HBC dissemination. A more complete understanding of the regulation of MMP-2-activator by type I collagen may provide new avenues for improved diagnosis and prognosis of human breast cancer.     

Lack of apoptosis in the hypoxic brain of a rat model mimicking cyanotic heart disease

OBJECTIVE: To assess the effect of chronic hypoxia on brain neuronal apoptosis, an animal model mimicking cyanotic heart disease was utilized. METHODS: Rats were placed in an hypoxic environment at birth and oxygen levels were maintained at 10% in an air-tight Plexiglass chamber. Controls remained in room air. Animals were sacrificed and the brains were harvested at 1 and 4 weeks, respectively. RESULTS: Significant polycythemia developed in the hypoxic rats at 1 and 4 weeks. Indexed brain mass to body weight was significantly increased in the hypoxic groups by 18% (p < 0.01) and 38% (p < 0.01) as compared to controls at 1 and 4 weeks, respectively. There was no difference in the number of apoptotic neurons between the chronically hypoxic rats and controls, as assayed by TUNEL labelling and Hoechst staining. The role of the sphingolipid ceramide was then examined because of its reported role in stress response, growth suppression and apoptosis. It was found that the brain ceramide accumulation was not significantly different in the hypoxic and control groups at 1 and 4 weeks. CONCLUSION: A protective adaptive response to chronic hypoxia in the neonatal brain may exist.     

The role of CT scan in laparoscopic retrieval of a perforated intrauterine device (IUD)

The intrauterine device (IUD) is a common modality of contraception in developing countries; it is inexpensive, effective, can be used for a long period of time and, most importantly, is reversible. An IUD may perforate through the uterine wall into the pelvic abdominal cavity or into adjacent organs. The common and accepted treatment for displaced IUDs is laparoscopic or surgical removal because of the possible risk of adhesion formation or damage to the intestine or urinary bladder. We report four cases of intra-abdominal IUDs that underwent successful extraction by laparoscopic surgery. All of our patients underwent a preoperative CT scan as it was more accurate in locating the device site and its relation to the surrounding organ and bowel. The CT scan gives more information, specifically, whether the device is extending into the bowel or urinary bladder.     

Emergency peripartum hysterectomy in Northern Jordan: indications and obstetric outcome (an 8-year review)

Objective To review cases of emergency peripartum hysterectomy regarding their incidence, risk factors, indications and complications and their results were carefully analysed.Materials and methods A retrospective study of cases of emergency peripartum hysterectomy which were performed in the period between February 1994 and February 2002 at the Princess Badeea Teaching Hospital in Northern Jordan. Demographic and clinical data were extracted and closely interpretedResults In the study period there were a 70,252 deliveries and 61 cases of emergency peripartum hysterectomies. The overall incidence was 0.87 peripartum hysterectomies per 1,000 deliveries. There were 50 cases (82%) delivered by caesarean section and 11 cases (18%) were delivered vaginally. Caesarean hysterectomy was performed in 50 cases and postpartum hysterectomy was performed in 11 cases. Total hysterectomy was performed in 39 cases (64%) and subtotal hysterectomy was performed in 22 cases (36%). The main indications for hysterectomy were morbidly adherent placenta (47.5%), ruptured uterus (27.9%) and uncontrollable haemorrhage from uterine atony (21.3%). There were two maternal deaths and 7 cases of stillbirths and 4 cases of early neonatal deaths.Conclusion Peripartum hysterectomy is a dramatic with high risk but a life saving operation. It is usually associated with significant maternal and fetal morbidity and mortality. Obstetricians should identify patients at risk and anticipate the procedure and complications, as early intervention and proper management facilitate optimal outcome.     

Serum Leptin Elevation in Obese Women with PCOS: A Continuing Controversy

PURPOSE: To evaluate leptin levels in a sample of obese women with PCOS and compare the results with obese and non-obese control, to be ultimately correlated with BMI, and insulin sensitivity. METHODS: Leptin and insulin assays by immuno-radiometric method, glucose assay by enzymatic colorimetric method. RESULTS: Leptin levels were significantly different between obese and non-obese subjects, and were significantly different between insulin resistant and non-insulin resistant obese PCOS, but were not significantly different between obese non-insulin resistant PCOS, and obese controls. CONCLUSIONS: Body mass index and insulin resistance are the two main factors governing serum leptin levels.