The Role of Vitamin D Supplementation Before Coronary Artery Bypass Grafting in Preventing Postoperative Atrial Fibrillation in Patients With Vitamin D Deficiency or Insufficiency: A Systematic Review and Meta-Analysis.

This study aims to evaluate the role of preoperative vitamin D supplementation before coronary artery bypass grafting (CABG) surgery in preventing postoperative atrial fibrillation (POAF) in vitamin D deficient or insufficient patients. Three randomized controlled trials (RCTs) comprising 448 subjects were selected after a detailed search was conducted on PubMed, Cochrane CENTRAL, Scopus, and Embase in December 2022. Analysis was run using RevMan (version 5.4.1; Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014). The analysis collected risk ratio (RR) and 95% confidence interval (CI) data from the relevant studies, which were then pooled using a random effects model. A significance level of less than 0.05 (p<0.05) was considered significant. Our analysis showed that compared with the standard of care, preoperative vitamin D supplementation in vitamin D deficient and insufficient patients effectively reduced POAF after CABG surgery (RR=0.6, 95% CI=0.4-0.9, P=0.01). There was no significant difference in the duration of hospitalization between the vitamin D supplementation group compared with the control following CABG (mean difference -0.85, 95% CI -2.13 to 0.43, P = 0.19). This meta-analysis shows that preoperative vitamin D supplementation in vitamin D deficient and insufficient patients undergoing CABG can reduce the rate of POAF. As POAF is associated with many complications, providing vitamin D supplementation to individuals with a vitamin D deficiency undergoing CABG can improve long-term cardiovascular outcomes following surgery.

A Cannabinoid CB1 Receptor-Positive Allosteric Modulator Reduces Neuropathic Pain in the Mouse with No Psychoactive Effects.

The CB1 receptor represents a promising target for the treatment of several disorders including pain-related disease states. However, therapeutic applications of Δ(9)-tetrahydrocannabinol and other CB1 orthosteric receptor agonists remain limited because of psychoactive side effects. Positive allosteric modulators (PAMs) offer an alternative approach to enhance CB1 receptor function for therapeutic gain with the promise of reduced side effects. Here we describe the development of the novel synthetic CB1 PAM, 6-methyl-3-(2-nitro-1-(thiophen-2-yl)ethyl)-2-phenyl-1H-indole (ZCZ011), which augments the in vitro and in vivo pharmacological actions of the CB1 orthosteric agonists CP55,940 and N-arachidonoylethanolamine (AEA). ZCZ011 potentiated binding of [(3)H]CP55,940 to the CB1 receptor as well as enhancing AEA-stimulated [(35)S]GTPγS binding in mouse brain membranes and ß-arrestin recruitment and ERK phosphorylation in hCB1 cells. In the whole animal, ZCZ011 is brain penetrant, increased the potency of these orthosteric agonists in mouse behavioral assays indicative of cannabimimetic activity, including antinociception, hypothermia, catalepsy, locomotor activity, and in the drug discrimination paradigm. Administration of ZCZ011 alone was devoid of activity in these assays and did not produce a conditioned place preference or aversion, but elicited CB1 receptor-mediated antinociceptive effects in the chronic constriction nerve injury model of neuropathic pain and carrageenan model of inflammatory pain. These data suggest that ZCZ011 acts as a CB1 PAM and provide the first proof of principle that CB1 PAMs offer a promising strategy to treat neuropathic and inflammatory pain with minimal or no cannabimimetic side effects.

The monoacylglycerol lipase inhibitor JZL184 suppresses inflammatory pain in the mouse carrageenan model.

AIM: The present study tested whether the selective monoacylglycerol lipase (MAGL) inhibitor JZL184 would reduce allodynia and paw edema in the carrageenan test. MAIN METHODS: The anti-edematous and anti-allodynic effects of JZL184 were compared to those of PF-3845, an inhibitor of fatty acid amide hydrolase (FAAH), and diclofenac, a non-selective cyclooxygenase inhibitor. Cannabinoid receptor involvement in the anti-edematous and anti-allodynic effects of JZL184 was evaluated by administration of the respective CB1 and CB2 receptor antagonists rimonabant and SR144528 as well as with CB1(-/-) and CB2(-/-) mice. JZL184 (1.6, 4, 16, or 40mg/kg) was administered for six days to assess tolerance. KEY FINDINGS: JZL184 administered before or after carrageenan significantly attenuated carrageenan-induced paw edema and mechanical allodynia. Complementary genetic and pharmacological approaches revealed that the anti-allodynic effects of JZL184 required both CB1 and CB2 receptors, but only CB2 receptors mediated its anti-edematous actions. Importantly, both the anti-edematous and anti-allodynic effects underwent tolerance following repeated injections of high dose JZL184 (16 or 40mg/kg), but repeated administration of low dose JZL184 (4mg/kg) retained efficacy. SIGNIFICANCE: These results suggest that the MAGL inhibitor JZL184 reduces inflammatory nociception through the activation of both CB1 and CB2 receptors, with no evidence of tolerance following repeated administration of low doses.

Variation in Fourier transform infrared spectra of some homeopathic potencies and their diluent media.

OBJECTIVE: The aim of this study was to determine whether potentized homeopathic drugs and their diluent media differ from each other with respect to their Fourier transform infrared (FTIR) spectra. DESIGN: FTIR spectra of Nux vomica 30C, Lycopodium 30C, Santonin 30C, Cina 30C, Cina 206C, Cina 1006C, and their diluent media 90% ethanol and Ethanol 30C were obtained in the wave number range of 2000-1000 cm1 at 20 degrees C. Potassium bromide powder soaked with the potencies, pressed into pellets, and air dried were used to measure the spectra. Because water structures in homeopathic potencies are thought to carry specific information on drug molecules and because O-H bending vibrational band (v2) exclusively belongs to water, the study was restricted to the bands in that wave number region. Alcohol has no absorption in the O-H bending region. RESULTS: The potencies were found to differ from each other and their diluent media in the number of v2 bands, their wave number (cm1), shape, and half-width (cm1) of the bands. CONCLUSIONS: The number and other characteristics of the v2 band represent the number of hydrogen-bonded water species and their hydrogen-bonding strength, respectively. The potencies and their diluent media therefore differ from each other in the number of hydrogen-bonded water species and their hydrogen-bonding strength. The observation that KBr pellets soaked with a potentized drug retains its specific spectral absorption properties simply confirms that medicated sucrose globules, used in homeopathic dispensing, are capable of retaining the therapeutic properties of the drug.

Reduction in the number of infective Trichinella spiralis larvae in mice by use of homeopathic drugs.

BACKGROUND: Trichinellosis caused by the gastrointestinal nematode Trichinella spiralis occurs in humans, domestic animals and wild animals. It is difficult to control the muscle phase of the parasite. Homeopathic drugs such as Cina and Santoninum have anthelmintic properties. We have observed that in material doses, the homeopathic drug Podophyllum also has nematotoxic properties. We have also observed that homeopathic potency can influence the water permeability of cells. OBJECTIVE: The purpose of this study was to investigate whether potentized homeopathic drugs such as Cina 30, Santoninum 30 and Podophyllum mother tincture can affect the muscle phase of the parasite T. spiralis in mice. Another objective was to see whether trichinellosis and its treatment with the 3 named homeopathic drugs could alter the water content in the muscle tissue of mice. MATERIALS AND METHODS: Cina 30 and Santoninum 30 were prepared from the mother tincture of the flowering tops of Artemisia nilagirica and its active principle santonin, in each case by successive dilution (1:100) with 90% ethanol and sonication in 30 steps following the single glass method (K30). Ethanol 30 was prepared by successive dilution of 90% ethanol with 90% ethanol (1:100) followed by sonication in 30 steps. In each step, the dilution was sonicated at 20 KHz for 30 s. We have observed before that sonication is a more uniform, measurable and effective process of mechanical agitation of a liquid than manual succussion. Experimentally infected mice were orally treated with an aqueous Podophyllum suspension at 60 mg/kg/day. Each potentized drug was diluted 1:20 with distilled water and administered orally at 0.05 ml/mouse/day. Each mouse was inoculated with T. spiralis larvae at a dose of 200 larvae/mouse by esophageal intubation. Treatment was started on day 7 post-infection and continued for 120 days. After completion of treatment, the mice were sacrificed and the larvae were extracted from muscles by HCl-pepsin digestion. The water content of the muscles was measured by determining the difference between fresh weight and dry weight of the tissue. RESULTS: Podophyllum Theta, Cina 30 and Santoninum 30 reduced the larval population in the studied mice by 68.14%, 84.10% and 81.20%, respectively, as compared to the untreated control group. Ethanol 30 achieved no significant reduction in the larval population compared to the untreated control group. The water content of the muscle tissue in the untreated control group and the Podophyllum-treated groups was significantly higher than in the Ethanol 30-, Cina 30- and Santoninum 30-treated groups. CONCLUSIONS: (1) Podophyllum Theta, Cina 30 and Santoninum 30 were effective in the muscle phase of T. spiralis infection and significantly reduced the larval population in the treated mice. The potencies were more effective than the mother tincture, an effect which was not due to the medium ethanol. (2) The potencies significantly reduced the water content of the muscle tissue which might have affected the larvae. The effect of Podophyllum Theta might be due to the direct toxic effect of the drug on the larvae.