Synthesis of novel acylated and esterified ciprofloxacin derivatives as efficient anticancer and antimicrobial agents

Nowadays, various factors enhance the resistance of some microbes to antibiotics. Irrational antibiotic use is considered an example of such factors. Therefore, the synthesis and reporting of heterocyclic compounds with multiple biological properties are of considerable value. Ciprofloxacin is an antibiotic used to treat infections. New amidification and esterification derivatives of ciprofloxacin were synthesized. Their structure was identified and confirmed using both proton and carbon-13 nuclear magnetic resonance, mass spectrometry, and elemental analysis. With the employment of MTT (3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl-terazoliumbromide) methods, in vitro anticancer activity was evaluated. The utilization of clinical and laboratory standards institute (CLSI) instructions was involved in the in vitro antimicrobial activity evaluation of the newly synthesized derivatives. In terms of anticancer activity, cell proliferation, viability, and IC50, as well as antimicrobial activities, IZD (Inhibition Zone Diameter), MIC (Minimum Inhibitory Concentrations), MBC (Minimum Bactericidal Concentrations), and MFC (Minimum Fungicidal Concentration) were measured and reported. The lowest cell proliferation and viability and IC50 for 2,3-dihydroxypropyl 1-cyclopropyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylate (compound 5) were observed to be 27.12% and 7.83 μg/mL. In antimicrobial activity, the lowest MIC for 2,3-dihydroxypropyl 7-(4-benzoylpiperazin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylate (compound 6c) was observed to be 2 μg/mL (against Proteus mirabilis) and the lowest MIC for 1-cyclopropyl-6-fluoro-7-(4-(4-(methylthio)benzoyl)piperazin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (compound 3d) was observed to be 32 μg/mL (against Candida albicans, Aspergillus fumigatus). The effects were compared with commercially available drugs, and it was observed that some derivatives have the same efficacy as abemaciclib, which is used to treat breast cancer. Some derivatives were more effective than Cefazolin and Tolnaftate, well-known antibiotics and antifungals, respectively. Finally, a fairly clear relationship between the structure of the derivatives and their biological effectiveness was observed

Sex Differences in Stress-Induced (Takotsubo) Cardiomyopathy

Background: Takotsubo cardiomyopathy (TC) affects predominantly women. Prior studies have suggested that men might have worse short-term outcomes, but limited data are available regarding long-term outcomes. We hypothesized that men, compared to women, with TC have worse short- and long-term outcomes. Methods: A retrospective study of patients diagnosed with TC between 2005 and 2018 in the Veteran Affairs system was performed. Primary outcomes were in-hospital death, 30-day risk of stroke, death, and long-term mortality. Results: A total of 641 patients were included (444 men [69%]; 197 women [31%]). Men had a higher median age (65 vs 60 years; P \u3c 0.001), and women were more likely to present with chest pain (68.7% vs 44.1%; P \u3c 0.001). Physical triggers were more common in men (68.7% vs 44.1%, P \u3c 0.001). Men had a higher in-hospital mortality rate (8.1% vs 1%; P \u3c 0.001). On multivariable regression analysis, female sex was an independent predictor for improved in-hospital mortality, compared to men (odds ratio 0.25, 95% confidence interval 0.06-1.10; P = 0.04). On 30-day follow-up, no difference occurred in a combined outcome of stroke and death (3.9% vs 1.5%; P = 0.12). On long-term follow-up (3.7 ± 3.1 years), female sex was identified as an independent predictor of lower mortality (hazard ratio 0.71, 95% CI 0.51-0.97; P = 0.032). Women were more likely to have TC recurrence (3.6% vs 1.1%; P = 0.04). Conclusions: In our study with a predominantly male population, men had less-favourable short- and long-term outcomes after TC, compared to those of women

Sex Differences in Stress-Induced (Takotsubo) Cardiomyopathy

BACKGROUND: Takotsubo cardiomyopathy (TC) affects predominantly women. Prior studies have suggested that men might have worse short-term outcomes, but limited data are available regarding long-term outcomes. We hypothesized that men, compared to women, with TC have worse short- and long-term outcomes. METHODS: A retrospective study of patients diagnosed with TC between 2005 and 2018 in the Veteran Affairs system was performed. Primary outcomes were in-hospital death, 30-day risk of stroke, death, and long-term mortality. RESULTS: A total of 641 patients were included (444 men [69%]; 197 women [31%]). Men had a higher median age (65 vs 60 years; P \u3c 0.001), and women were more likely to present with chest pain (68.7% vs 44.1%; P \u3c 0.001). Physical triggers were more common in men (68.7% vs 44.1%, P \u3c 0.001). Men had a higher in-hospital mortality rate (8.1% vs 1%; P \u3c 0.001). On multivariable regression analysis, female sex was an independent predictor for improved in-hospital mortality, compared to men (odds ratio 0.25, 95% confidence interval 0.06-1.10; P = 0.04). On 30-day follow-up, no difference occurred in a combined outcome of stroke and death (3.9% vs 1.5%; P = 0.12). On long-term follow-up (3.7 ± 3.1 years), female sex was identified as an independent predictor of lower mortality (hazard ratio 0.71, 95% CI 0.51-0.97; P = 0.032). Women were more likely to have TC recurrence (3.6% vs 1.1%; P = 0.04). CONCLUSIONS: In our study with a predominantly male population, men had less-favourable short- and long-term outcomes after TC, compared to those of women

LONG TERM OUTCOMES OF TAKOTSUBO CARDIOMYOPATHY IN MEN COMPARED TO WOMEN IN THE US VETERAN AFFAIRS HEALTHCARE SYSTEM

Background: Takotsubo cardiomyopathy is characterized by significant transient left ventricular dysfunction. Differences in long term outcome in men compared to women is not well described in the literature. Methods: We performed a retrospective study using chart review for patients diagnosed with Takotsubo Cardiomyopathy between 2005 and 2018 in the Veteran Affairs (VA) national database. We included patients who met the Mayo Clinic diagnostic criteria for Takotsubo Cardiomyopathy. We compared the long term outcomes in men vs women patients. Results: 641 patients were included, of those 69.3% were males, median age was 64 years, median ejection fraction at the time of diagnosis was 35. On Kaplan-Meier analysis there was no significant difference between men and women in the rates of recurrence of Takotsubo at median follow up of 4 years, or arrhythmia at 1 year (Figure-1 A and B respectively). However, men had higher mortality rate over 10 year follow up period (Figure-1 C). Conclusion: In patients with Takotsubo cardiomyopathy at the VA system, men had higher mortality rates but there was not significant difference in rates of recurrence or arrhythmias when compared to women

Cryoballoon vs radiofrequency ablation of atrial fibrillation: insights from the Veterans Healthcare System

PURPOSE: Catheter ablation is considered the mainstay treatment for drug-refractory atrial fibrillation (AF). The aims of our study were to compare the efficacy and safety of the most two currently approved approaches (point-by-point radiofrequency ablation (RFA), either with contact force (CF) or without contact force (nCF) catheters, and cryoballoon ablation (CBA)) in the Veterans Healthcare System. METHODS: We performed a retrospective study of patients who underwent ablation for treatment of AF at the veterans affairs healthcare system between 2013 and 2018. Only the first reported ablation procedure was included. RESULTS: We included 956 patients in the study (97.4% males, 91.5% Caucasians, 67% paroxysmal AF), with 682 patients in RFA-nCF, 139 in RFA-CF, and 135 in CBA. Thirty-day complication rates were comparable between the three groups with the exception of higher incidence of phrenic nerve injury in CBA group when compared to RFA-nCF (2.2% vs 0.0%, p \u3c 0.01). Long-term recurrence rate of AF was significantly lower in the CBA group when compared to RFA-nCF (33.3% vs 47.7%, adjusted HR 0.60, 95% CI 0.44-0.83, p \u3c 0.01). On the other hand, it was similar between RFA-CF and RFA-nCF groups (43.9% vs 47.7%, adjusted HR 1.01, 95% CI 0.76-1.33, p 0.97). After stratifying patients based on AF type, these findings were only present in patients with paroxysmal AF. CONCLUSION: CBA for paroxysmal AF, in male dominant patients\u27 population, was associated with lower incidence of AF recurrence rate while having a comparable safety profile to RFA independent of the use of CF catheters

Predetermined Anti-Diabetic Drug Regimen Adjustments during Ramadan Fasting: An Observational Study of Safety

BackgroundMany Muslim type 2 diabetes mellitus (T2DM) patients choose to fast the month of Ramadan despite the possible adverse health effects brought about by the change in dietary habits, among other things. Clinical data regarding the safety of multi-drug regimens during fasting are particularly scarce. The aim of the study was to evaluate the safety of a drug protocol devised by the authors to accommodate Ramadan's dietary changes, involving dose adjustments of four anti-diabetic drug regimens in T2DM patients fasting Ramadan.MethodsIn this prospective, observational, open-label study, 301 T2DM patients who wished to fast Ramadan were followed during Ramadan and the preceding month. The incidence of hypoglycemia, diabetic ketoacidosis (DKA) and non-ketotic hyperosmolar state (NKHS) was monitored. Patients were classified into four groups: A group (those taking metformin, sulfonylurea and insulin [n=33]); B group (metformin and sulfonylurea [n=89]); C group (metformin and insulin [n=96]); and D group (premixed 70/30, glargine or regular insulin [n=82]). During Ramadan, drug doses were adjusted as percentages of their pre-Ramadan values: 75% for sulfonylureas, 75% for glargine, 75% for premixed insulin 70/30 in two doses, and 75% for regular insulin. Metformin was adjusted to a twice-daily regimen.ResultsNo cases of DKA or NKHS were reported. Hypoglycemia occurred at a lower rate than pre-Ramadan values in groups C, and D; and a similar rate in groups A, and B.ConclusionThe data suggested that using the above protocol to adjust the doses of anti-diabetic drugs is safe in T2DM patients in regards to hypoglycemia, DKA, and NKHS