Development and validation of UPLC-PDA method for concurrent analysis of bergenin and menisdaurin in aerial parts of Flueggea virosa (Roxb. ex Willd.)

Bergenin and menisdaurin are biologically active components which are found in plant Flueggea virosa (Phyllanthaceae). Bergenin has pharmacological actions such as chemopreventive and antihepatotoxic while menisdaurin has an anti-viral activity which needs its evaluation by an analytical method (UPLC-PDA method) that can be applied to the quality control of pharmaceutical preparations. The developed UPLC-PDA method was applied for identification and quantification of standards bergenin and menisdaurin in the methanol extract of F. virosa (FVME). The analysis was carried out using Eclipse C18 (4.6?×?100?mm, 3.5?µm) UPLC column. The optimized chromatographic condition was achieved at 0.16?mL/min flow rate using gradient system with acetonitrile and water as mobile phase. Both biomarkers were measured at λ_max 235?nm in PDA detector at ambient temperature. The developed method furnished sharp and intense peaks of menisdaurin and bergenin at Rt?=?2.723 and 3.068?min, respectively along with r2?>?0.99 for both. The recoveries of bergenin and menisdaurin were found in the range of 99.37–101.49% and 98.20–100.08%, respectively. With other validation data, including precision, specificity, accuracy, and robustness, this method demonstrated excellent reliability and sensitivity. The separation parameters i.e. retention, separation, and resolution factors for resolved standards (bergenin and menisdaurin) were >1, which showed good separation. The quantity of bergenin and menisdaurin in the FVME sample was found as 15.16 and 3.28% w/w, respectively. The developed UPLC-PDA method could be conveniently adopted for the routine quality control analysis.     

Comparison of peri‐implant clinical and radiographic status around short (6 mm in length) dental implants placed in cigarette‐smokers and never‐smokers: Six‐year follow‐up results

Background

It is hypothesized that peri‐implant clinical and radiographic inflammatory parameters (probing depth [PD], bleeding on probing [BOP] and plaque index [PI]; and radiographic (crestal bone loss [CBL]) are worse among cigarette‐smokers (CS) compared with never‐smokers (NS) with short implants.

Purpose

The present 6‐year follow‐up retrospective study compared the peri‐implant clinical and radiographic parameters in CS and NS with short dental implants (6 mm in length).

Materials and methods

Fifty‐six male individuals were included. These individuals divided into 2 groups as follows: (a) Group‐1: 29 self‐reported systemically healthy CS with 48 short‐implants; and (b) Group‐2: 27 self‐reported systemically healthy NS with 43 short implants. Peri‐implant PD, PI, BOP, and CBL were measured. Group comparisons were done using the Kruskal‐Wallis test and sample size was estimated. Level of significance was set at P values < .05.

Results

In groups 1 and 2, the follow‐up durations were 6.2 ± 0.1 years and 6.1 ± 0.3 years, respectively. A cigarette smoking history of 8.9 ± 3.6 pack years was reported by individuals in Group‐1. At follow‐up, scores of peri‐implant PD, BOP, PI, and mesial and distal CBL were comparable around short implants in both groups.

Conclusion

Under strict oral hygiene maintenance protocols, short dental implants can remain functionally stable in CS in a manner similar to NS.     

Association between sex hormones and migraine in young Saudi females

Objectives:To assess the sex hormone levels in young Saudi female migraineurs during a migraine attack and during pain-free periods and compare them with control subjects.Methods:A case-control study involving 14 Saudi female migraineurs and 21 control subjects was conducted between December 2019 and March 2020. Demographic and disease history data were collected through participant interviews. Blood samples were drawn during the migraine attack and pain-free periods.Results:Follicular (30.00±19.60; p<0.001) and luteal (39.79±11.45; p=0.037) estrogen levels were significantly higher in patients with non-menstrual related migraine (NMM), while luteal testosterone levels (1.10±0.31; p=0.023) were significantly higher in patients with menstrually related migraine (MM). Body mass index (BMI) was higher in patients with NMM (25.77±6.53; p=0.013), and it was found to be associated with follicular estrogen (p=0.016), progesterone (p=0.018), and pain intensity (p=0.042). Luteal estrogen level was significantly lower (13.96±7.88; p=0.036) in patients with luteal onset of attack.Conclusion:High estrogen levels were found to mediate NMM, their effect being more pronounced with increase in BMI; whereas low luteal estrogen levels mediated MM. Young females with MM might have high luteal testosterone levels, and a compensatory protective role could be surmised accordingly.     

Behaviour change interventions to improve medication adherence in patients with cardiac disease: Protocol for a mixed methods study including a pilot randomised controlled trial

Background

Suboptimal adherence to medication increases mortality and morbidity; individually tailored supportive interventions can improve patients’ adherence to their medication regimens.

Musculoskeletal pain among male faculty members of the College of Medicine and College of Dentistry

We aimed to establish the local prevalence of musculoskeletal pain among faculty members in Saudi Arabia and describe the patient''s risk factors and preventive measures that may reduce its burden.An observational, quantitative, cross-sectional study was carried out to evaluate the prevalence of musculoskeletal pain and its risk factors among male faculty members in the College of Medicine and Dentistry, using a designed questionnaire based on the Standardized Nordic Musculoskeletal Questionnaire. Chi-square testing at a significance level of P < .05, was used for comparative analysis. SPSS version 26 was used for all analyses.Ninety responders participated in the survey analysis. The prevalence of musculoskeletal pain among faculty members was 77.8%, and the most common site of musculoskeletal pain occurred at two different sites of the three (low back, neck, and shoulder), with a prevalence of 38.9%. As for risk factors of musculoskeletal pain, only age group showed a significant correlation with the site of musculoskeletal pain (P = .024), where patients in the younger age group (25–35 years old) were at higher risk of lower back pain, while participants in the older age group (36 to 44 years old and 45 years or older) were at higher risk of musculoskeletal pain in two different sites.Musculoskeletal pain affects more than two-thirds of faculty members. In particular, low back pain is a common problem among faculty members. Age is a significant risk factor for the occurrence of musculoskeletal pain, with more than one site involvement in older age.     

1,2,3-Triazole–quinazolin-4(3H)-one conjugates: evolution of ergosterol inhibitor as anticandidal agent

The present study describes the synthesis of 1,2,3-triazole–quinazolinone conjugates (5a–q) from ethyl 4-oxo-3-(prop-2-ynyl)-3,4-dihydroquinazoline-2-carboxylate and phenyl azide/substituted phenyl azides employing Cu(i) catalysed Huisgen 1,3-dipolar cycloaddition. The corresponding acids (6a–q) were obtained by hydrolysis of esters (5a–q) to study the effect of these functionalities on the biological activity. All synthesized compounds were screened for in vitro anticandidal evaluation against Candia albicans, Candida glabrata and Candida tropicalis strains. The results indicated that compound 5n showed potent anticandidal activity with IC₅₀ in the range of 8.4 to 14.6 μg mL⁻¹. Hemolytic activity using human red blood cells (hRBCs) and cytotoxicity by MTT assay on human embryonic kidney (HEK-293) cells revealed the non-toxic nature of the selected compounds. Growth kinetic study with compound 5n showed its fungicidal nature as no significant growth of Candida cells was observed even after 24 h. Cellular ergosterol content was determined in the presence of different concentrations of 5n to measure the activity of lanosterol 14α-demethylase indirectly. The results showed significant disruption of the ergosterol biosynthetic pathway through inhibition of lanosterol 14α-demethylase activity supported by docking studies (PDB: 5v5z). Overall, this study demonstrates the anticandidal potential of 5n which can serve as the lead for further structural optimization and SAR studies.

The present study elicits the synthesis of 1,2,3-triazole–quinazolinone conjugates (5a–q) as ergosterol inhibitors for Candida infections.     

Plant-derived antiviral drugs as novel hepatitis B virus inhibitors: Cell culture and molecular docking study

Despite high anti-HBV efficacies, while the nucleoside analogs (e.g., lamivudine) lead to the emergence of drug-resistance, interferons (e.g., IFN-α causes adverse side-effects. Comparatively, various natural or plant products have shown similar or even better efficacy. Hence, new antiviral strategies must focus not only on synthetic molecules but also on potential natural compounds. In this report, we have combined the in vitro cell culture and in silico molecular docking methods to assess the novel anti-HBV activity and delineate the inhibitory mechanism of selected plant-derived pure compounds of different classes. Of the tested (2.5-50?μg/ml) twelve non-cytotoxic compounds, ten (10?μg/ml) were found to maximally inhibit HBsAg production at day 5. Compared to quercetin (73%), baccatin III (71%), psoralen (67%), embelin (65%), menisdaurin (64%) and azadirachtin (62%) that showed high inhibition of HBeAg synthesis, lupeol (52%), rutin (47%), β-sitosterol (43%) and hesperidin (41%) had moderate efficacies against HBV replication. Further assessment of quercetin in combination with the highly active compounds, enhanced its anti-HBV activity up to 10%. Being the most important drug target, a 3-D structure of HBV polymerase (Pol/RT) was modeled and docked with the active compounds, including lamivudine as standard. Docking of lamivudine indicated strong interaction with the modeled HBV Pol active-site residues that formed stable complex (?G?=??5.2?kcal/mol). Similarly, all the docked antiviral compounds formed very stable complexes with HBV Pol (?G?=??6.1 to ?9.3?kcal/mol). Taken together, our data suggest the anti-HBV potential of the tested natural compounds as novel viral Pol/RT inhibitors.     

Hypoglycemia associated with carcinoid tumors. A case report and review of the literature

The authors report a 73-year-old man with a jejunal carcinoid tumor and spontaneous hypoglycemia. Plasma insulin was suppressed (insulin/glucose ratio, 0.2), and nonsuppressible insulin-like proteins (NSILP) were elevated. Seven other patients with carcinoid or related tumors associated with hypoglycemia were found in the literature. Nonsuppressible insulin-like proteins were not measured in these patients.     

Results of intravenous steroid injection on reduction of postoperative edema in rhinoplasty

Objective

To determine the efficacy of intravenous dexamethasone in reducing postrhinoplasty edema.

Design

A prospective, randomized clinical trial with placebo control.

Setting

Department of Otorhinolaryngology, Al-Sabah and Zain Hospital, Kuwait.

Subject

Eighty-four patients (male = 28; female = 56) aged between 20 and 40 years, undergoing open rhinoplasty with hump removal and bilateral lateral osteotomies were enrolled in this study.

Intervention

Patients were randomized to receive two doses of 10 mg of dexamethasone intravenously or placebo, first dose during surgery and second dose 12 hours after surgery.

Main outcome measures

Patients were evaluated postoperatively at 24 hours, days 2, 5, 7 and 10 for periorbital edema.

Results

10 mg of dexamethasone given intravenously during rhinoplasty and a second dose 12 hours after surgery, reduced postoperative periorbital edema significantly.

Conclusion

This study showed a statistically significant benefit of dexamethasone over placebo in reducing periorbital edema after rhinoplasty. No complications were attributed to the administration of dexamethasone.