The anti-inflammatory properties of vinpocetine mediates its therapeutic potential in management of atherosclerosis.

Atherosclerosis (AS) formation is enhanced by different mechanisms including cytokine generation, vascular smooth muscle cell proliferation, and migration. One of the recent treatments towards endothelial dysfunction and AS is Vinpocetine (VPN). VPN is a potent inhibitor of phosphodiesterase enzyme 1 (PDE-1) and has anti-inflammatory and antioxidant effects through inhibition the expression of nuclear factor kappa B (NF-κB). VPN has been shown to be effective against the development and progression of AS. However, the underlying molecular mechanism was not fully clarified. Consequently, objective of the present review was to discuss the mechanistic role of VPN in the pathogenesis AS. Most of pro-inflammatory cytokines that released from macrophages are inhibited by action of VPN through NF-κB-dependent mechanism. VPN blocks monocyte adhesion and migration by constraining the expression and action of pro-inflammatory cytokines. As well, VPN is effective in reducing of oxidative stress a cornerstone in the pathogenesis of AS through inhibition of NF-κB and PDE1. VPN promotes plaque stability and prevents the erosion and rupture of atherosclerotic plaque. In conclusion, VPN through mitigation of inflammatory and oxidative stress, and improvement of plaque stability effects could be effective agent in the management of AS.

Conjugated Linoleic Acid-Carboxymethyl Chitosan Polymeric Micelles to Improve the Solubility and Oral Bioavailability of Paclitaxel.

Oral delivery, the most common method of therapeutic administration, has two significant obstacles: drug solubility and permeability. The challenges of current oral medicine delivery are being tackled through an emerging method that uses structures called polymeric micelles. In the present study, polymeric micelles were developed using conjugates of linoleic acid-carboxymethyl chitosan (LA-CMCS) for the oral delivery of paclitaxel (PCL). The developed micelles were evaluated by particle size, zeta potential, Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). When PCL was contained within micelles, its solubility increased by almost 13.65 times (around 60 µg/mL). The micelles' zeta potentials were -29 mV, their polydispersity indices were 0.023, and their particle diameters were 93 nm. Micelles showed PCL loading and entrapment efficiencies of 67% and 61%, respectively. The sustained release qualities of the PCL release data from micelles were good. In comparison to the pure PCL suspension, the permeability of the PCL from micelles was 2.2 times higher. The pharmacokinetic data revealed that PCL with LA-CMCS micelles had a relative bioavailability of 239.17%, which was much greater than the PCL in the suspension. The oral bioavailability of PCL was effectively increased by LA-CMCS micelles according to an in vivo study on animals. The polymer choice, maybe through improved permeability, plays an essential role when assessing oral bioavailability enhancement and solubility improvement (13.65 times). The outcomes demonstrated that PCL's solubility and pharmacokinetics were improved in the micelles of the LA-CMCS conjugate.

Connecting Pharmacists and Other Health Care Providers (HCPs) towards Drug Therapy Optimization: A Pharmaceutical Care Approach.

Background: Pharmaceutical care services offered by pharmacists rationalize drug therapy, improve patient quality of life, and save patients' lives. This study was designed to optimize patient drug therapy through pharmaceutical care services offered by a pharmacist in consultation with other health care providers (HCPs) at a tertiary care hospital. Methods: This descriptive study was conducted to assess the role and effectiveness of pharmacists in optimizing drug therapy outcomes. The study was carried out at an internal and pulmonary medicine unit of a tertiary care hospital in Srinagar, Jammu and Kashmir, India, with a total of 50 health care providers (HCPs) (24 doctors, 16 nurses, and 10 pharmacists). A total of 182 patients (males and females) of all age groups were recruited into the study over a period of nine months. Patient-specific pharmaceutical care plans initiated by the pharmacist based on drug therapy-related needs and problems were used to address and optimize drug therapy outcomes in consultation with other HCPs. Results: A total of 388 drug-related problems (DRPs) with an average of 2.29 DRPs per patient were identified, for which 258 pharmaceutical care plans as interventions were proposed, out of which 233 (90.31%) were accepted and implemented. Preassessment and postassessment by HCPs on services rendered by the pharmacist showed a positive change in attitude among HCPs with respect to their endorsement and acceptance of the pharmacist's services in providing direct patient care. Conclusions: Pharmaceutical care services offered by pharmacists helped in optimizing drug therapy and patient care.

Demographic and clinical variations of keratoconus in Saudi population.

PURPOSE: The aim of this prospective study was to identify the demographic and clinical variations of keratoconus (KC) in Saudi Arabia. METHODS: A self-administered survey was completed by patients in Saudi hospitals. The survey included questions on demographics, educational level, treatment options, dry eye, eye rubbing because of allergy, residence, family history, and consanguineous marriage. RESULTS: Six hundred and forty-eight patients (375 - male, 273 - female; mean age: 26.89 [standard deviation: 7.04] years; range: 11-50 years) were conducted at 13 central hospitals in all 13 administrate areas of Saudi Arabia over a 1-year period. Five hundred and forty-three (83.8%) patients had a secondary school diploma or diploma's degree of education and mostly were from the Aseer and Riyadh regions. The geographical distribution rate of KC was highest in the mountainous areas. For dry eye, 21.9% and 44.8% of the patients, respectively, reported frequent or occasional dryness and 13.4% and 48.9% of the patients, respectively, reported frequent or occasional bouts of eye allergy. Furthermore, 17.9% and 61.9% of the patients, respectively, reported that they constantly or sometimes rubbed their eyes. Marriages were endogamous in 53.5% of the patients and the family history was positive by 56.8%. There was a history of ocular disease in 27% of the patients and the systemic disease was 13%. CONCLUSION: This study is the first to describe the regional demographic and clinical variations of KC in Saudi Arabia. Its findings suggest that the different distribution of keratoconic patients between provinces is attributable to genetic and/or environmental factors.

Prevalence of cardiovascular events among patients with type 2 diabetes in the west region of Saudi Arabia.

Background: Diabetes mellitus (DM) remains a concern globally and particularly in Saudi Arabia, where its prevalence is continuously increasing among the Saudi population. DM is known to increase the risk of cardiovascular disease (CVD), which can progress significantly if DM is poorly controlled. Aim: Determine the prevalence of cardiovascular events among patients with type 2 diabetes (T2DM) in the west region of Saudi Arabia, and additionally the use of antidiabetic agents with cardiovascular benefits (ADc) in T2DM patients with cardiovascular events (CVEs). Method: A retrospective cohort study was conducted among all patients with T2DM who presented to the diabetic center of Prince Mansour Military Hospital (PMMH), Taif city, between the 1st of January and 30th of June 2021. Data extracted from patient medical records included demographics, home medications, medications used to treat T2DM, lab results, and ECG data. Descriptive statistics were used to analyze and compare the results. The study was approved by the Research and Ethics Committee of Medical Services General Directorate, Armed Forces Hospitals, Taif region. Result: A total of 349 patients with T2DM were recruited and included in the final analysis. Of this study population, 132 patients had experienced at least one cardiovascular event while 54 were considered to be at risk of future cardiovascular events due to having risk factors for cardiovascular diseases above and beyond the presence of diabetes. A subgroup analysis was conducted to examine HbA1c% among all groups; interestingly, all were similar, with p > 0.05. Of all diabetic patients with CVEs, only 34.8 % were on at least one anti-diabetic agent known to have cardiovascular benefits; the remainder were on other anti-diabetic agents. A similar analysis was conducted on diabetic patients with risk of CVEs, of which only 13 % were on at least one anti-diabetic agent having known cardiovascular benefits; the remainder were on other anti-diabetic agents. Conclusion: The prevalence of CVEs among T2DM patients in Saudi Arabia is very close to the global prevalence, but ADcs are underutilized in this population. Tighter glycemic control is warranted to help rein in and reduce the CVE incidence among patients with T2DM.

Letrozole targets the human ether-a-go-go-related gene potassium current in glioblastoma.

Aberrant expression of human ether-a-go-go-related gene (hERG) potassium channels has been implicated in the pathophysiology of glioblastoma (GBM). Letrozole has demonstrated efficacy in pre-clinical GBM models. The objective of this research was to assess the potential for hERG inhibition by letrozole to mediate efficacy in GBM. hERG currents were assessed using patch-clamp electrophysiology in an overexpression system during treatment with letrozole, exemestane or vehicle (dimethyl sulphoxide). Relative to vehicle, peak hERG tail current density was reduced when treated with 300 nmol/L and 1 µmol/L letrozole but not when treated with exemestane (up to 1 µmol/L). Cell proliferation was assessed in cultured glioblastoma cell lines (U87 and U373) treated with letrozole, exemestane, doxazosin (hERG blocker) or vehicle. Letrozole, but not exemestane, reduced cell proliferation relative to vehicle in U87 and U373 cells. The associations between expression of hERG (KCNH2), aromatase (CYP19A1) and the oestrogen receptors (ESR1 and ESR2) and time to all-cause mortality were assessed in GBM patients within The Cancer Genome Atlas (TCGA) database. hERG expression was associated with reduced overall survival in the TCGA GBM cohort. Future work is warranted to investigate hERG expression as a potential biomarker to predict the therapeutic potential of hERG inhibitors in GBM.

MicroRNA 362-3p Reduces hERG-related Current and Inhibits Breast Cancer Cells Proliferation.

BACKGROUND/AIM: hERG potassium channels enhance tumor invasiveness and breast cancer proliferation. MicroRNA (miRNA) dysregulation during cancer controls gene regulation. The objective of this study was to identify miRNAs that regulate hERG expression in breast cancer. MATERIALS AND METHODS: Putative miRNAs targeting hERG were identified by bioinformatic approaches and screened using a 3'UTR luciferase assay. Functional assessments of endogenous hERG regulation were made using whole-cell electrophysiology, proliferation assays, and cell-cycle analyses following miRNA, hERG siRNA, or control transfection. RESULTS: miR-362-3p targeted hERG 3'UTR and was associated with higher survival rates in patients with breast cancer (HR=0.39, 95%CI=0.18-0.82). Enhanced miR-362-3p expression reduced hERG expression, peak current, and cell proliferation in cultured breast cancer cells (p<0.05). CONCLUSION: miR-362-3p mediates the transcriptional regulation of hERG and is associated with survival in breast cancer. The potential for miR-362-3p to serve as a biomarker and inform therapeutic strategies warrants further investigation.