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.     

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.     

COVID‐19 reinfection or reactivation in a renal transplant patient

Recurrences of COVID‐19 infection may occur in immunocompromised patients. Reinfection or reactivation of COVID‐19 virus is a challenging issue in these patients.     

Design and testing of statistical methods to classify the severity of steppage gait based on center of pressure data

In this research kinematics parameters derived from ground reaction forces were evaluated to limit differential diagnoses and measure the degree of disabilities during walking among neuropathic subjects. 25 neuropathic subjects affected by drop foot and 20 normal subjects were enrolled in the study. Each subject was tested in average 10±2 times for calculating kinetics parameters derived from ground reaction forces. The results revealed that the center of pressure displacement pattern in sole of foot can be a good index for differential diagnoses and measuring the degree of disabilities. This research can extend the clinical applications of ground reaction force plate and introduce suitable criteria to measure the degree of disability among neuropathic patients.     

Cerebral phaeohyphomycosis due to Rhinocladiella mackenziei in Persian Gulf region: A case and review

Cerebral phaeohyphomycosis is frequently a fatal disease caused by truly neurotropic dematiaceous fungi. Although rare, this infection occurs especially among immunocompetent patients, and the clinical symptoms are often misdiagnosed as a cerebral tumour or bacterial brain abscess. The appropriate diagnosis and therapy of cerebral infections by melanized fungi are very challenging if they are caused by mysterious fungi with unknown ecological niche. We reported the second case of cerebral phaeohyphomycosis due to Rhinocladiella mackenziei in Iran and the first culture‐confirmed case. In this report, the differential diagnosis and histopathological findings are discussed and a review of the literature is provided.     

Changes in biophysical characteristics of PFN1 due to mutation causing amyotrophic lateral sclerosis

Metabolic Brain Disease - Single amino acid mutations in profilin 1 (PFN1) have been found to cause amyotrophic lateral sclerosis (ALS). Recently, we developed a mouse model for ALS using a PFN1...     

A Comprehensive Review on Pharmacotherapeutics of Three Phytochemicals,Curcumin, Quercetin,and Allicin,in the Treatment of Gastric Cancer

Objective

Gastric cancer is one of the most common causes of cancer-related death worldwide. Medicinal plants are one of the main sources for discovery of new pharmacological agents especially for treatment of cancers. The aim of the present study is to review pharmacotherapeutic aspects of three mostly studied phytochemicals including curcumin, quercetin, and allicin for management of gastric cancer.

Methods

Scopus, PubMed, Web of Science, and Google Scholar were searched for the effects of curcumin, quercetin, allicin, and their analogs in gastric cancer. Data were collected up to November 2015. The search terms were “curcumin,” “quercetin,” “allicin,” and “gastric cancer” or “cancer.”

Results

Curcumin demonstrated anti-angiogenic, anti-proliferative, anti-metastatic, pro-apoptotic, and anti-helicobacter activities. Quercetin inhibited cell growth and induced apoptosis, necrosis, and autophagy as well as anti-Helicobacter activity. Allicin showed apoptotic and anti-Helicobacter properties. All three natural compounds had low bioavailability.

Conclusions

Although preclinical studies demonstrated the activity of curcumin, quercetin, and allicin in gastric cancer, clinical trials are needed to confirm their effectiveness. Applying their possible synergistic action and suitable drug delivery system in clinical studies can be also an attractive approach with the purpose of finding new extremely efficient anti-gastric cancer agents.

Mini-Abstract

Curcumin, quercetin, and allicin seem to be good candidates for management of gastric cancer through their pro-apoptotic, anti-proliferative, and anti-helicobacter activities.

     

Intranasal ketamine reduces pain of digital nerve block; a double blind randomized clinical trial

BackgroundLow dose ketamine can be used as analgesic in acute pain management in the emergency department (ED).ObjectiveEfficacy of IN ketamine in acute pain management in the ED.MethodThis is a double blind randomized clinical trial on patients older than 15 years who needed digital nerve block (DNB). Participants randomly received IN Ketamine (1 ml = 50 mg) or placebo (normal saline, 1 ml) 5 min before DNB. In both groups, patients' pain score was recorded by visual analogue score (VAS) at baseline, after DNB and 45 min after completion of DNB. Adverse effects of ketamine and changes in vital signs were also recorded and compared with placebo group.ResultsA total number of 100 patients were enrolled in the study with the median (IQR) age of 36.5 (26) years, including 65 men and 35 women. IN ketamine resulted in less pain compared to placebo after performing DNB and 45 min after the procedure. Median (IQR) basic VAS score was 50 (15) in ketamine group, and 49 (27) in control group. Median (IQR) block pain VAS score was 28.5 (19) in ketamine group and 47.5 (31) in control group. Median (IQR) procedural pain VAS score was 21.5 (16) in ketamine group and 43.5 (29) in control group. Only 7 patients had adverse effects in either group.ConclusionThe findings of this study suggest that IN ketamine can be effective in reducing pain in patients with acute pain, without adding significant side effects.