Additive effects of CD59 expression in Gal knockout mice in vitro but not in an ex vivo model

Abstract: Transgenic expression of the human complement regulatory molecule CD59 in mice and genetic deletion of the major xenoantigen galactose α 1,3 galactose (Gal KO) each resulted in partial protection of spleen cells from lysis by human serum. These protective effects were additive when the two genetic modifications were combined. However, when the effects of these genetic modifications were examined in an ex vivo model in which mouse hearts were perfused with human plasma, it was Gal KO which was the modification which determined protection. CD59 expression alone was not protective and CD59 expression in combination with Gal knockout did not result in a significant additional increase in protection over and above that provided by Gal knockout alone. The likely explanation for this discrepancy between the in vitro and ex vivo data is that the H2-K^b promoter used to drive CD59 expression results I in substantially less expression on endothelium than on spleen cells.     

Combined effects of caffeine and malnutrition on the newborn rat's myocardium.

We hypothesized that the pathological effects on the neonatal rat heart could be aggravated by Cu deficiency due to the combined effects of caffeine exposure and malnutrition. Upon birth, pups were mixed and randomly picked; 8 pups were assigned to each dam and then divided into 4 groups. Group 1 dams received a normal diet containing 20% protein. Group 2 dams were fed 20% protein diet supplemented with caffeine (4 mg/100 g BW). Group 3 dams received 6% protein diet as a malnourished group, and group 4 dams received 6% protein diet supplemented with caffeine (4 mg/100 g BW). On postnatal day 10, dams and pups were killed. Group 2 tended to have a decrease in the Cu levels of dams' plasma and milk and in pups' plasma and heart tissue compared to those of group 1. This pattern was not observed consistently between groups 3 and 4. Transmission electron microscopy of group 2 pups' hearts revealed a degree of disruption in the mitochondria compared to normal mitochondria seen in group 1. There was no consistent change in the mitochondria of group 4 compared to group 3. The caffeine level observed in all categories of group 4 (dams' plasma and milk, pups' plasma and heart tissue) was lower than those in group 2. Although malnutrition affected body weight and heart weight, combined effects of caffeine and malnutrition on Cu content in the neonatal heart was relatively minor compared to the well nourished group. This well nourished group showed that the effects of caffeine on Cu were more consistent, resulting the changes of mitochondria.     

Flixweed vs. Polyethylene Glycol in the Treatment of Childhood Functional Constipation: A Randomized Clinical Trial

Background:

Polyethylene glycol (PEG) is often considered as the first-line treatment for functional constipation in children. Descurainia sophia (L.) Webb et Berth (D. sophia) is a safe recommended medicine in Iranian folk and Traditional Persian Medicine for the treatment of constipation.

Objectives:

To clinically compare D. sophia with PEG 4000 (without electrolyte) in pediatric constipation and to assess its efficacy and side effects.

Patients and Methods:

120 patients aged 2 - 12 years with constipation for at least 3 months were included in an 8 weeks lasting randomized controlled trial within two parallel-groups. Children received either PEG, 0.4 g/kg/day, or D. sophia seeds, 2 grams (for children aged 2 - 4 years) and 3 grams (for those aged > 4 years) per day.

Results:

A total of 109 patients completed the study (56 in D. sophia and 53 in PEG group). At the end of the study, 36 (64.3%) patients in D. sophia group and 29 (54.7%) in PEG group were out of Rome III criteria (P = 0.205). Median weekly stool frequency in 0, 1, 2, 3 weeks of the treatment was found to be 2, 5, 5, 5 in D. sophia and 3, 4, 4, 5 in PEG group (P = 0.139, 0.076, 0.844, 0.294), respectively. The number of patients who suffered flatulence was less (5, 8.9%) in D. sophia group as compared to PEG group (6, 11.3%) at the end of the trial (P = 0.461). D. sophia taste was less tolerated.

Conclusions:

D. sophia is introduced as a cheap and available medication which can be applied as a safe alternative to conventional PEG in the management of pediatric chronic functional constipation.     

Mannich bases derived from lawsone and their metal complexes: synthetic strategies and biological properties

Lawsone (2-hydroxynaphthalene-1,4-dione) is a natural product which shows significant biological activity. Aminomethylnaphthoquinone Mannich bases derived from lawsone constitute an interesting class of naphthoquinones and/or their metal complexes have demonstrated a series of important biological properties. So, this review aimed to document the publications concerning the synthesis of aminomethylnaphthoquinone Mannich bases from lowsone, aldehydes and amines and their metal complexes using different conditions, and investigation of their applications.

Lawsone (2-hydroxynaphthalene-1,4-dione) is a natural product which shows significant biological activity.     

Pentoxifylline: A Drug with Antiviral and Anti-Inflammatory Effects to Be Considered in the Treatment of Coronavirus Disease 2019

In December 2019, a new coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged from China, causing pneumonia outbreaks first in the Wuhan region and has now spread worldwide. There are no specific drugs for the disease caused by this virus, coronavirus disease 2019 (COVID-19). Considering that new synthesized drugs cannot be applied immediately to patients, conventional drug in new use is a feasible solution. Chloroquine, remdesivir, favipiravir, lopinavir, ribavirin, and ritonavir have shown efficacy to inhibit coronavirus in vitro. Pentoxifylline, a drug with anti-inflammatory, immunomodulatory, and bronchodilatory effects, has previously been shown to inhibit several viral infections. Immunological studies have shown that most patients with severe COVID-19 exhibit substantially elevated serum levels of pro-inflammatory cytokines. Pentoxifylline is a phosphodiesterase inhibitor that increases the levels of cyclic adenosine monophosphate, which in turn activates protein kinase, leading to a reduction in the synthesis of pro-inflammatory cytokines and immune cell migration. Here, we propose pentoxifylline, a drug with low cost and toxicity, as a possible treatment for COVID-19 based on its interesting properties.     

Photobiomodulation therapy reduces apoptotic factors and increases glutathione levels in a neuropathic pain model

Neuropathic pain (NP) is caused by damage to the nervous system due to reactive oxygen spices (ROS) increase, antioxidants reduction, ATP production imbalance, and induction of apoptosis. In this investigation, we applied low-level laser 660 nm (photobiomodulation therapy) as a new strategy to modulate pain. In order to study the effects of photobiomodulation therapy (660 nm) on NP, chronic constriction injury (CCI) model was selected. Low-level laser of 660 nm was used for 2 weeks. Thermal and mechanical hyperalgesia were measured before and after surgery on days 7 and 14, respectively. Paw withdrawal thresholds were also evaluated. Expression of p2x3, Bax, and bcl2 protein was measured by western blotting. The amount of glutathione (GSH) was measured in the spinal cord by continuous spectrophotometric rate determination method. The results are presented as mean?±?SD. Statistical analysis of data was carried out using SPSS 21. CCI decreased the pain threshold, 2-week photobiomodulation therapy significantly increased mechanical and thermal threshold, decreased P2X3 expression (p?<?0.001), and increased bcl2 expression (p?<?0.01), but it was not effective on the Bax expression. We speculated that although photobiomodulation therapy increased ROS generation, it increased antioxidants such as GSH. Increase in bcl2 is another mitochondrial protection mechanism for cell survival and that pain relief and decrease in P2X3 expression confirm it.     

Epicardial Versus Endocardial Pacemakers in the Pediatric Population: A Comparative Inquiry

Background: Most children in need of cardiac pacemakers remain dependent on the function of the permanent from childhood to adulthood. We sought to evaluate and compare the function between epicardial and endocardial pacemakers in pediatric groups with different conditions. Methods: Between 2012 and 2018, this single-canter study evaluated 44 pediatric patients with indications for epicardial or endocardial pacemakers. Results: The 2 groups, at a median age of 5 (0.1–16) years, were compared concerning the characteristics of the leads used (n = 80: bipolar, unipolar, steroid-eluting, and non–steroid-eluting), survival data, and complications. The reason for pacemaker implantation was congenital complete heart block in 11 (25%) cases and postoperative heart block in 33 (75%) cases. The commonest congenital heart disease accompanied by postoperative block was the ventricular septal defect. In the endocardial lead group, the mean ventricular pacing threshold immediately after the implantation and during the follow-up was less than that in the epicardial lead group (0.75 vs. 0.81 V; P = 0.01 and 0.8 vs. 2.4 V; P = 0.001). During the follow-up, the mean battery longevity was better in the endocardial group (last visit: 6.7 endocardial vs. 3.3 years epicardial). Lead failure was commoner in the epicardial pacemaker, and chronic high-pacing threshold pattern was seen in 14 patients in this group. After 3 years, freedom from lead failure was 94% and 63% in the endocardial and epicardial leads. Conclusions: Pacemakers with endocardial bipolar steroid-eluting leads showed better lead characteristics regarding survival and battery longevity than epicardial pacemakers without these lead characteristics. An appropriate pacemaker type should be selected based on the patient’s condition.