Several studies have reported a relation between increased pro-inflammatory mediators such as TNF-α and apoptosis in neurodegenerative diseases such as Alzheimer’s disease (AD). It is known that lipopoly-saccharide (LPS) treatment induces neuroinflammation and memory deterioration, and it has been reported that LPS induces apoptosis mostly through the production of TNF-α. Pentoxifylline (PTX), is a vascular protective agent and a potent TNF-alpha inhibitor. However, the molecular neuroprotective mechanisms of PTX against LPS-induced neurotoxicity have not been well studied. In this study, we investigated the direct protective effect of PTX against LPS-induced toxicity in Rat pheochromocytoma (PC12) cell line. The results showed that a pretreatment with PTX prior exposure to LPS signifycantly decreased LPS-induced cell death. Mechanisms study showed that PTX has the potential to inhibit pro-inflammatory and pro-apoptotic pathways via the suppression of TNF-α and a caspase-dependent pathway in neuronal PC12 cells. This is the first study to report the anti-inflammatory and anti-apoptotic effects of PTX via inhibition of TNF-α and a caspase-dependent pathway in neuronal PC12 cells. Altogether, these observations indicate that PTX is capable of promoting neuroprotective effects, meanwhile also present some insights into the potential signaling pathways that are involved. Thus, these findings support the potential for PTX to be investigated as a potential agent for the treatment of neurodegenerative diseases such as AD

Background: Long-term therapy for chronic obstructive pulmonary disease (COPD) is progressing fast. Dual bronchodilation with long-acting muscarinic antagonist (LAMA) and long-acting β2-agonist (LABA) fixed dose combinations (FDC) have been available over the past few years. To evaluate the real-world tolerability and effectiveness of formoterol plus glycopyrronium FDC inhaler, a post-marketing surveillance study was conducted in Indian population.Methods: This was an open-label, observational registry in which COPD patients, who were prescribed forglyn (a brand of FDC of glycopyrronium 25 mcg and formoterol fumarate dihydrate 6 mcg dry powder inhalation). The effectiveness, safety and tolerability of this LAMA/LABA combination were evaluated for 4, 8 and 12 weeks. The safety and tolerability was assessed based on the incidence of adverse events (AEs). Effectiveness was evaluated based on change in total symptom score from baseline to end of 12 weeks. The forced expiratory volume in 1 second (FEV1) was performed at baseline and end of 12 weeks.Results: Total COPD patients enrolled were 605, of which 78.5% were males and 21.5% were females. Patients showing improvement of symptoms at week 4 were 587 (97.02%).Overall, at the end of 8 week and 12 week 98.34 % and 99.49% patients showed improvement in the total symptoms respectively. About 0.49% did not show any improvement. AEs were reported in 64 (10.64%) patients with no serious AEs. Mean FEV1 of 476 patients before treatment was 1.53±0.68 L at baseline which changed to 1.85±4.74 L at the end of 12 weeks, with was statistically significant (p<0.05).Conclusions: In real-life clinical practice in India, formoterol and glycopyrronium FDC dry powder inhaler was well tolerated in COPD patients, and can be regarded as an effective option for maintenance treatment.

Background: Type 2 diabetes mellitus (T2DM) is a progressive disease with multifactorial aetiology. Metformin monotherapy is commonly used as the initial treatment, but is often inadequate in achieving optimal glycaemic control, necessitating the need of second and third-line therapies. Fixed dose combination (FDC) of dapagliflozin and sitagliptin in Indian setting is gaining popularity. Time-in-target has become a useful blood glucose indicator that goes "beyond HbA1c" to understand glycaemic control in people with diabetes better. Aims and Objectives: To assess the efficacy of a FDC of dapagliflozin and sitagliptin in Indian T2DM patients. Materials and Methods: This was a single-arm, single-centre, real-world study. Twenty-eight consented T2DM patients age >18 years, either sex, not hospitalized, and estimated glomerular filtration rate >60 ml/min/1.73m2 were administered a continuous glucose monitoring system (CGMS) (Freestyle Libre Pro). Once daily fixed-dose combination (FDC) of dapagliflozin (10mg) and sitagliptin (100mg) was given along with CGMS administration on a background of existing therapy for those who were not to target for glycemic parameters. Since the FDC reaches at its peak concentration after 3-4 days of administration, the efficacy of FDC was considered from 5th day. Hence the baseline was calculated taking the mean of first 4 days after FDC administration. Patients' characteristics, including age (years), sex, weight (kg), body mass index (kg/m2), estimated glycated haemoglobin (%), history of oral hypoglycaemic agents, and dose of insulin were recorded. For efficacy assessment, average daily glucose (ADG), time in target (TIT), time below target (TBT), and time above target (TAT) were recorded at baseline.) and end of the study (day 15th of CGMS administration) from the daily glucose summary of Freestyle Libre Pro CGMS. The percentage improvement of each efficacy parameters were assessed. Results: A statistically significant improvement (p<0.05) in ADG (19.41% decrease), TIT (34.47% increase), and TAT (31.13% decrease) was observed, whereas TBT was increased by 29.23%. Mean age (n=28), weight (n=23), body mass index (n=19) and estimated HbA1c (n=19) was 56.70±9.8 years, 64.67±9.52 Kg, 24.99±4.23 Kg/m2 and 6.84±1.63 % respectively. The majority were on triple drug (n=14; 50%) therapy before CGMS administration than dual (n=5; 17.9%) and monotherapy (2; 7.1%). Fifteen (53.8%) were on insulin with a mean insulin dose of 16.40 IU. Conclusion: Once daily FDC of dapagliflozin and sitagliptin in Indian T2DM patients significantly improves AGD, TIT, and TAT at the end of 15 days.

Inflammatory immune mechanisms play a central role in the pathogenesis of Alzheimer's disease (AD). Recent reports have established the role of TNF‐alpha in neuronal dysfunction. This study evaluated the neuroprotective effects of pentoxifylline, phosphodiesterase E4 inhibitor, in LPS‐treated PC12 cells. Cells were pretreated with varying doses of Pentoxifylline (0.1–1mM) for 2 hours before stimulation with LPS for 48 hours. Cell viability increased with 1 mM pentoxifylline, as measured with MTT assay. Furthermore, western blot analysis showed a dose‐dependent reduction in the expression of TNF‐alpha. In parallel, agarose gel electrophoresis demonstrated that neurotoxicity induced with LPS triggered apoptosis (characterized by DNA fragmentation) and pentoxifylline exerted its protective effect through inhibition of the apoptotic pathway (reduction in DNA fragmentation). This anti‐apoptotic effect of Pentoxifylline was confirmed by the decrease in the expression of pro‐apoptotic protein Bad, the increase in the expression of antiapoptotic protein BcL2 on western blot analysis, and the reduction of caspase 3 levels as measured by caspase‐3 assay. The present study indicates that Pentoxifylline may be a promising approach for the treatment of AD, through inhibition of apoptosis. Study supported by LIU‐College of Pharmacy.

Background and Objective: Cardiovascular disease (CVD) is a significant cause of morbidity and mortality worldwide, with high-risk patients requiring effective management to reduce their risk of cardiovascular events. Bempedoic acid is a novel therapeutic agent recently approved as an add-on therapy to statins in patients with uncontrolled LDL-c. Bempedoic acid inhibits cholesterol synthesis in the liver, which ultimately reduces the risk of cardiovascular events. Therefore, the present study aims to assess the efficacy and safety of bempedoic acid in patients with uncontrolled LDL-c (Previously on moderate or high-intensity statins) with a high risk of CVD in real-world settings. Methods: This is a multicenter, retrospective, observational study on the data of high-risk-CVD patients collected from Bempedoic Acid on Efficacy and Safety in patients (BEST) Registry. The clinical data of 140 patients who were already on statin therapy and were receiving Bempedoic acid at a dose of 180 mg, along with measurements of the level of LDL-c, HbA1c, HDL, TG, TC, PPPG, FPG, AST, ALT, serum creatinine was taken into consideration. The primary outcome includes a change in LDL-c level, and secondary outcomes involve a change in the level of HbA1c, HDL, TG, TC, PPPG, FPG, AST, ALT, and serum creatinine at week 12 and 24. Adverse events were reported at both time points. Results: A total of 140 patients were included in the present study with a mean age of 51.8 ± 9.2 years and had primary confirmed diagnosis of dyslipidemia with uncontrolled LDL-c. The mean levels of LDL-c decreased from the mean baseline value of 142.67 ± 46.49 mg/dL, to 106.78 ±33.92 mg/d; a statistically significant reduction by 23.23% (p < 0.01) at week 12. Similarly, at week 24, the mean LDL-c value reduced to 90.39 ± 38.89 mg/dL. A 33.38 % decrease was observed (p < 0.01). Other parameters such as non-HDL, FPG, PPPG, AST and serum creatinine also showed statistically significant reduction at week 12 and week 24.  Conclusion: The present study demonstrates that bempedoic acid is an effective add-on medication in lowering LDL-c levels in high-risk CVD patients with uncontrolled LDL-c.