Bringing back Galium aparine L. from forgotten corners of traditional wound treatment procedures: an antimicrobial, antioxidant, and in-vitro wound healing assay along with HPTLC fingerprinting study.

BACKGROUND: The wound healing process, restoring the functionality of the damaged tissue, can be accelerated by various compounds. The recent experimental analysis highlights the beneficial effects of phytochemicals in improving skin regeneration and wound healing. In traditional medicine, one of the widespread plants used for treating different injuries or skin afflictions is Galium aparine L. (GA). Besides, previously reported chemical compounds of GA suggested its therapeutic effects for the wound healing process, yet its regulatory effects on the cellular and molecular stages of the wound healing process have not been investigated. METHODS: In the present study, the phytochemical profile of the GA extract was analyzed using HPTLC fingerprinting, and further scientific evaluation of its phytochemicals was done. The wound-healing effects of GA extract were explored at the cellular and molecular levels while accounting for cell toxicity. The wound closure enhancing effect, antibacterial activity, and antioxidant activity were assessed. RESULTS: The HPTLC fingerprinting of the GA extract proved its previously reported phytochemical profile including phenols, flavonoids, tannins, plant acids, ergot alkaloids, flavonoids, anthraquinones, terpenoids, sterols, salicin, lipophilic compounds, saponins, iridoids, and heterocyclic nitrogen compounds. Antimicrobial assessment, of the extract, indicated the more susceptibility of S. aureus to the inhibitory effects of GA rather than E. coli and S. epidermidis. DPPH test results revealed the antioxidant property of GA extract, which was comparable to ascorbic acid. The results of the viability assay showed no cytotoxicity effects on human umbilical endothelial cell (HUVEC) and normal human dermal fibroblast (NHDF) cell lines treated with different concentrations of whole plant extract and cell viability increased in a dose-dependent manner. The results of the scratch assay showed improved cell migration and wound closure. CONCLUSIONS: This study shows the anti-oxidant, anti-microbial, and in vitro wound healing wound-healing effects of GA hydroalcoholic extract, which aligns with its use in traditional medicine. No cytotoxicity effects were shown. The results from this study can be the basis for further investigations such as animal models and phytochemical studies. Further evaluation of its effects on mechanisms and signaling pathways involved in the wound healing processes such as angiogenesis and cell proliferation can provide novel insights into the potential therapeutic effects of the GA extract.

Formulation of sumatriptan succinate orodispersible tablets using chitosan and sodium starch glycolate for immediate migraine relief.

Migraine is one of the common neurological disease affecting around 23% of the Pakistani population. Prompt treatment is required to regain the functional ability of patients. The present study was designed to develop sumatriptan succinate orodispersible tablets that would quickly overcome acute migraine episodes using 22 full-factorial design. The chitosan and sodium starch glycolate were taken as independent variables; friability, disintegration, dispersion time and water absorption ratio as response variables. Eight trial formulations were generated by Design Expert® software. The main effect plots were used to check the interaction of formulations with response variables. All trial formulations showed good micromeritic properties in terms of angle of repose (19.59o-24.57°), Carr's index (17.08-24.90%) and Hausner's ratio (1.20-1.33). The tablets wetted quickly (17.1- 39 sec) in dispersion medium, showed higher water absorption ratio (188-341 sec) and disintegrated quickly (13-20 sec) with an excellent dissolution rate (94-99%). The main effect plots show interactions between the independent variables against most of the study responses. A 22 full-factorial model was found to be effective in studying the influence of formulation variables on response parameters. Both chitosan and sodium starch glycolate can be used in combination to fabricate an effective orodispersible formulation of sumatriptan succinate.

Long-term outcomes of titanium-nitride-oxide coated stents and drug-eluting stents in acute coronary syndrome: A systematic review and meta-analysis.

BACKGROUND: In severe cases of coronary artery disease, percutaneous coronary intervention provide promising results. The stent used could be a drug-eluting stent (DES) or a titanium-nitride-oxide coated stent (TiNOS). AIM: To compare the 5-year effectiveness and safety of the two stent types. METHODS: The following systematic review and meta-analysis was conducted in accordance with the preferred reporting items for systematic reviews and meta-analysis guidelines, and PubMed/MEDLINE, Scopus, and Cochrane Central were searched from inception till August 2023. Primary outcomes were major adverse cardiac events (MACE), cardiac death, myocardial infarction (MI), cardiac death or MI, and ischemia-driven total lesion revascularization (ID-TLR). RESULTS: Four randomized controlled trials (RCT), which analyzed a sum total of 3045 patients with acute coronary syndrome (ACS) after a median follow-up time of 5 years were included. Though statistically insignificant, an increase in the ID-TLR was observed in patients receiving TiNOSs vs DESs. In addition, MI, cardiac death and MI, and definite stent thrombosis (DST) were significantly decreased in the TiNOS arm. Baseline analysis revealed no significant results with meta-regression presenting non-ST elevated MI (NSTEMI) as a statistically significant covariate in the outcome of MACE. CONCLUSION: TiNOS was found to be superior to DES in terms of MI, cardiac death or MI, and DST outcomes, however, the effect of the two stent types on ID-TLR and MACE was not significant. A greater number of studies are required to establish an accurate comparison of patient outcomes in TiNOS and DES.

Association of Visfatin gene polymorphism with obesity related metabolic disorders among Pakistani population: a case control study.

In recent years, the global prevalence of obesity and its associated metabolic disorders has reached alarming levels, presenting a significant challenge to public health worldwide. Visfatin, also known as pre-B cell colony-enhancing factor (PBEF) or nicotinamide phosphoribosyltransferase (NAMPT), is an adipokine that has been implicated in various physiological processes, including glucose homeostasis, lipid metabolism, and inflammation. The main objective of this proposed study is to find out the association between visfatin genetic variants and metabolic syndrome. The sample size of the study consisted of 300 blood samples (150 control and 150 cases). This study found that the genotypic frequency of visfatin SNPs, including rs2302559 (OD: 18.222; 95% CI 10.228-32.466; p-value < 0.001) and rs1215113036 (OD: 129.40; 95% CI 44.576-375.693; p-value < 0.001) were significantly associated with metabolic syndrome. Moreover, the frequency of the mutant alleles of both visfatin SNPs was found to be higher in patients with metabolic syndrome as compared to controls. Results of the current study indicate that people with any genetic variation of Visfatin, such as rs2302559 and rs1215113036, are more likely to develop metabolic syndrome. Visfatin genetic variants are linked to an increased risk of metabolic syndrome, implying it's role in disease pathophysiology.

A novel synthetic derivative of biaryl guanidine as a potential BACE1 inhibitor, to treat Alzheimer's disease: In-silico, in-vitro and in-vivo evaluation.

BACE1 enzyme has been known a potential target involved in Alzheimer's disease (AD). Present research was focused on the principles of virtually screening, chemical synthesis and protease inhibitory effect of BACE1 enzyme via biaryl guanidine derivatives. In-silico based paradigm (ligand binding interaction within active domain of BACE 1 enzyme i.e., aspartate Asp32 and Asp228) a novel compound was synthesized and subsequently subjected to in-vitro and in-vivo evaluation. 1,3-di(isoquinolin-6-yl) guanidine was synthesized and found potent (IC50 6±0.56 µM) and active to arrest (99 %) ß-secretase enzyme (FRET assay). Furthermore, it was found to improve novel object recognition test (RTI =56.55%) and Morris water maze test (32.26±3.45s) significantly (p<0.05). Enhanced pharmacokinetics and related properties (high iLOGP and Log S =-3.98) along with improved permeation to the blood brain barrier (BBB) (zero Lipinski violation) made it feasible to inhibit BACE1 as a novel therapeutic source to treat AD in future.

Influence of Prunus domestica gum on the release profiles of propranolol HCl floating tablets.

Propranolol hydrochloride is a beta-blocker used for the management and treatment of hypertension, angina, coronary artery disease, heart failure, fibrillation, tremors, migraine etc. The objective of the present study was to design Propranolol Hydrochloride floating tablets by direct compression method and to explore the role of a new gum as a matrix former. A 22 full factorial design was selected for the present study. Prunus domestica gum and HPMC (K4M) were used as independent variables, swelling index and drug dissolution at 12 hours as dependent variables. Formulations were subjected to pre- and post-compression tests that showed good micromeritics and buoyancy characteristics (Carr's index 11.76%-14.00%, Hausner's ratio 1.13°-1.16°, angle of repose 22.67°-25.21°, floating lag time 56-76 seconds, total floating time 18-25 hours and swelling index 59.87%-139.66%). The cumulative drug release in 0.1 N HCl at 12 hours was 72%-90% (p<0.05). Weibull model was found to be the best fit model (R2>0.99) among all other studied models. Multiple regression showed a significant effect of Prunus domestica gum and HPMC K4M on the swelling index and dissolution profiles of propranolol HCl (p<0.05). On the basis of better in-vitro performance and cost-effectiveness, formulation F4 was the best formulation. It is evident from the results that Prunus domestica gum possesses excellent drug release retardant potential for the floating drug delivery system and this new gum should be further explored alone or with other natural and synthetic polymers in future studies.

The effects of Ginsenosides on PI3K/AKT signaling pathway.

Ginsenosides belong to a group of steroid glycosides that are extracted from the plant genus Panax (ginseng). This plant has been used for a long time for the treatment of a variety of disorders in traditional medicine. Recent studies have assessed the biological impact of Ginsenosides in cell culture or animal models. Animal studies have shown their beneficial impacts in the remedy of pathological conditions in different tissues. The ameliorating effects of Ginsenosides in diverse pathogenic conditions can be attributed to their effects on the production of reactive oxygen species. These substances mainly affect the activity of AMPK/AKT and PI3K/AKT pathways. The beneficial effects of Ginsenosides have been appraised in diabetes-related complications, spinal cord injury, cerebral ischemia, myocardial ischemia, and other disorders which are associated with oxidative stress. Moreover, these substances have been shown to interfere with the pathologic conditions during carcinogenesis. In the current study, we explain these impacts in two distinct sections including non-neoplastic conditions and neoplastic conditions.

A comparative study on the effect of propolis and dentine bonding agent in treating dentine hypersensitivity.

OBJECTIVE: To find out if there is a difference in the efficacy of propolis and seventh-generation dentine bonding agent in reducing dentine hypersensitivity. METHODS: The randomised, single-blind study was conducted at the Department of Periodontology, Dow International Dental College, Dow University of Health Sciences, Karachi, from December 2018 to November 2019, and comprised patients with complaint of dentine hypersensitivity who were divided in group A which received 30% ethanolic extract of propolis, and group B which received dentine bonding agent. Recordings of dentine hypersensitivity were obtained at baseline, before and after the application of experimental agents, and on days 7, 15 and 30. The response was measured using the Schiff Cold Air Sensitivity Scale. Data was analysed using SPSS 20. RESULTS: Of the 52 patients, 19 (36.5%) were males and 33 (63.5%) were females. The overall mean age was 29.9 ± 6.5 years. Majority of the subjects were students i.e. 16 (30.8%) and housewives i.e. 11 (21.2%), while drivers, teachers, businessmen etc. constituted of 25 (48%) subjects. Significant reduction of dentine hypersensitivity was observed in both groups (p<0.05). Intergroup comparison showed non-significant differences (p>0.05). CONCLUSIONS: Propolis and dentine bonding agent had significant effect in reducing dentine hypersensitivity. The difference between the two was not significant.

Formulation development and in-vitro evaluation of gastroretentive drug delivery system of loxoprofen sodium: A natural excipients based approach.

The limitations of conventional type delivery systems to retain drug (s) in the stomach has resulted in the development of novel gastroretentive drug delivery system. We developed single-layer effervescent floating tablets of loxoprofen sodium for prolong delivery in the stomach using natural polymers xanthan gum, guar gum and semisynthetic polymer HPMCK4M. All the formulations (F1-F9) were developed by varying concentrations of xanthan gum and HPMCK4M while guar gum concentration was kept constant. Two gas generating agent (s) incorporated were sodium bicarbonate and citric acid. All compendial pre and post-compression tests results were in the acceptable limits. FTIR analysis confirmed drug-polymer compatibility. The in-vitro drug release in simulated conditions i.e., 0.1 N HCl for 12 h revealed orderly increase in total floating time, i.e., less than 6 h for F1 over 12 h for F9. Formulations F1 to F4 were not capable to retard drug release up to 12 h, whereas F5-F7 for 12 h, while F8 and F9 for more than 12 h. Data fitting in various kinetic models showed that drug release best fit in first order kinetic model and F9 in zero order. Based on results data, F7 was the best among all.

Presentations and Outcomes of Thyroid Storm.

The aim of this study is to describe the characteristics and outcome of thyroid storm patients presenting at two tertiary care centres of Karachi, i.e. at Dow University of Health Sciences; and Liaquat National Hospital, Karachi, from December 2018 to May 2019. All patients between 18-70 years of age, who were admitted with thyroid storm and fulfilled the Burch- Wartofsky criteria, were inducted. Demographics including age, gender, clinical presentations, systemic symptoms, clinical examination of the thyroid and laboratory findings were reviewed from the file records to identify factors associated with mortality using the available data. Overall, five (62.5%) out of eight patients were female. The mean age was 43 ±1.67 years. Infections were the most common comorbid condition followed by cardiovascular and gastrointestinal diseases. The in-hospital mortality rate was 87.5% (n=07).

Erupt of malaria, dengue and chikungunya in Pakistan: Recent insights about prevalence, diagnosis and treatment.

Malaria, dengue and chikungunya are the most rampant mosquito-borne infections predominantly in Pakistan. They pose a serious threat and cause a havoc for the victims owing to the life threatening signs and symptoms marked with elevated morbidity and mortality rate. It seems hard to discriminate due to common indications, consequently, deserves appropriate diagnosis prior elevated toll of death. Present article encompasses depth insights about their prevalence, diagnosis and clinical manifestation if erupt in the pandemic. However, host-vector-host cycle is the root cause of transmission and diverse mosquito species confer dissimilar infections. Indeed these infections are seasonal but other factors like flood, open irrigation channels, immense agricultural land, rich fauna and water reservoirs can't be overlooked. Dire need was felt to acknowledge and aware the public about local transmission, vector control, entomologic, research resources, diagnosis and advancement in healthcare system to alleviate them absolutely in future.

Directly compressed rosuvastatin calcium tablets that offer hydrotropic and micellar solubilization for improved dissolution rate and extent of drug release.

The objective was to use caffeine and Soluplus® to improve the dissolution rate and to maintain a concentration of BCS Class II rosuvastatin calcium that exceeds its solubility. Caffeine and Soluplus® together substantially improved the dissolution rate and the extent of rosuvastatin release. Formulations for direct compression tablets included Formulation F1, a control with drug but with neither caffeine nor Soluplus® present; F2 with drug-caffeine complex; F3 with drug and Soluplus® and F4 with drug-caffeine complex and Soluplus®. Each formulation blend provided satisfactory flow properties. Tablets were comparable in mass, hardness and friability. A marked decrease in disintegration time occurred when the hydrotropic or micellar agent was included in the formulation. Assay (98-100%) and content uniformity (99-100%) results met requirements. Release studies in pH 1.2, 6.6, and 6.8 buffers revealed the superiority of F4. At 45 min sampling time, F3 and F4 tablets each provided a cumulative drug release greater than 70% in each medium. F2 tablets exhibited compliance to official standards in pH 6.6 and 6.8 buffers but not in pH 1.2 buffer, whereas tablets based on F1 failed in each medium. Two-factor ANOVA of the release data revealed a statistical difference across the four formulations in each release medium. Pairwise comparison of release profiles demonstrated that, of the four formulations, F4 provided the most effectively enhanced dissolution rate, improvement to the extent of drug release and support of a concentration higher than the solubility of rosuvastatin calcium.

Lethal toxic Dose (i.p LD50), total protein contents and comparative hemolytic potential of (99mTc labeled & non-labeled) Naja naja karachiensis venom.

Recent recognition about snake bite envenomation on June, 2017 as neglected tropical disease under category-A by World Health Organization advocated again its undeniable importance. Present circumstances reasoned to work on a neglected subspecies of Naja naja, i.e., Naja naja karachiensis (N. n. karachensis) has been documented for frequent deaths in Pakistan. In this study median lethal toxic dose (LD50) was determined intraperitoneally in Swiss albino mice and was found to be 2.0µg/g (2.0mg/kg) equal in potency to Naja pallida (red spitting African cobra). Total protein contents (188±0.011µg / 200µg of dry weight) were high enough (94%) to represent an arsenal of proteins. Furthermore, 99mTc was labeled 99.9% with venom and didn't find to alter hemolytic activity of venom in dose dependent manner at 125µg/ml (p>0.5), 250 µg/ml (p>0.1) and 500 µg/ml (p>0.1) when compared with its crude form. Present work will pave the way for proteomics study in effective production of antidote against specific species of snakes as dare demand of it has been felt since long period of time in Pakistan.

FOXO Transcriptional Factors and Long-Term Living.

Several pathologies such as neurodegeneration and cancer are associated with aging, which is affected by many genetic and environmental factors. Healthy aging conceives human longevity, possibly due to carrying the defensive genes. For instance, FOXO (forkhead box O) genes determine human longevity. FOXO transcription factors are involved in the regulation of longevity phenomenon via insulin and insulin-like growth factor signaling. Only one FOXO gene (FOXO DAF-16) exists in invertebrates, while four FOXO genes, that is, FOXO1, FOXO3, FOXO4, and FOXO6 are found in mammals. These four transcription factors are involved in the multiple cellular pathways, which regulate growth, stress resistance, metabolism, cellular differentiation, and apoptosis in mammals. However, the accurate mode of longevity by FOXO factors is unclear until now. This article describes briefly the existing knowledge that is related to the role of FOXO factors in human longevity.

Formulation design and evaluation of Cefuroxime axetil 125 mg immediate release tablets using different concentration of sodium lauryl sulphate as solubility enhancer

Cefuroxime axetil immediate release tablets were formulated by direct compression method with different percentages of sodium lauryl sulphate (SLS) such as 0.5, 1.0, 1.5 and also without SLS. Resulting batches of tablets were evaluated by both pharmacopeial and non-pharmacopeial methods to ascertain the physico-mechanical properties. Dissolution test were carried out in different medium like 0.07 M HCl, distilled water, 0.1M HCl of pH 1.2 and phosphate buffers at pH 4.5 and 6.8 to observe the drug release against the respective concentration of SLS used. Later, test formulations were compared by f1 (dissimilarity) and f2 (similarity) factors using a reference brand of cefuroxime axetil. Significant differences (p<0.05) in dissolution rate were recorded with the change in concentration of SLS in different media. Test formulation T3 containing 1% SLS was found to be best optimized formulation based on assay, disintegration, dissolution and similarity and dissimilarity factors.

Formularam-se comprimidos de liberação imediata à base de cefuroxima axetil, pelo método de compressão direta, com diferentes percentagens de lauril sulfato de sódio (LSS), tais como 0,5, 1,0, 1,5, e também sem SLS. Os lotes resultantes dos comprimidos foram avaliados por ambos os métodos da farmacopeia e não farmacopeicos para determinar as propriedades físico-mecânicas. O teste de dissolução foi realizado em meios diferentes, como HCl 0,07 M, água destilada, HCl 0,1 M com pH 1,2 e os tampões fosfato (pH 4,5 e 6,8) para observar a liberação do fármaco contra a correspondente concentração de LSS utilizado. Em seguida, as formulações de teste foram comparadas por fatores f1 (dissimilaridade) e f2 (similaridade), utilizando uma marca de referência de cefuroxima axetil. Diferenças significativas (p<0,05) na taxa de dissolução foram registradas com a mudança na concentração de LSS em diferentes meios de dissolução. A formulação T3 contendo LSS a 1% foi considerada a melhor formulação otimizada com base nos ensaios de desintegração, dissolução e fatores de semelhança e dissimilaridade.

Antimicrobial activity of erythromycin and clarithromycin against clinical isolates of Escherichia coli, Staphylococcus aureus, Klebsiella and Proteus by disc diffusion method.

Fifty clinical isolates comprising of Escherichia coli, Staphylococcus aureus, Klebsiella and Proteus were collected from different local pathological laboratories and their resistant pattern against two well known macrolides; erythromycin and clarithromycin were studied using disc diffusion method. Klebsiella (41.67% against erythromycin and 58.34% against clarithromycin) and Proteus (66.67% against erythromycin and clarithromycin) species were found to be more resistant against the studied macrolides as compared to the rest of organisms. In case of Staphylococcus aureus and Escherichia.coli, resistant found were 27.78% and 23.54% against erythromycin and 22.23% and 35.30% against clarithromycin respectively. It is concluded from these figures that microbial resistance against these macrolides are increasing in our population which is alarming and therefore it is recommended to physicians to prescribe these antibiotics unless no other substitute is available in clinical practices.

Bioequivalence studies of two brands of meloxicam tablets in healthy Pakistani volunteers.

The pharmacokinetic parameters of two oral formulations of meloxicam tablets were compared in a randomized, single oral dose; two treatments cross over design in 12 healthy male volunteers belonging to Pakistan under fasting conditions. After an overnight fast, the volunteers received 30 mg meloxicam and the blood samples were collected up to 96 hours and drug concentrations were determined by a validated HPLC method. Various pharmacokinetic parameters were determined from the plasma concentration-time curves of both formulations. The 90% confidence intervals obtained by analysis of variance were 87-94% for C(max) and 88-97% for AUC(0-t), that fell well within the acceptance range of 80-125%. Also, no significant difference (a=0.05, Wilcoxon Signed rank test) were detected between T(max) of both formulations. The two formulations were well tolerated and no adverse effect was reported during the study.