By Injection Research Articles

The use of Oral Anti-Diabetic Medications in Diabetes Mellitus type 1: An Educational Article and Expert Opinion

Diabetes mellitus type 1 is lifelong condition resulting from failure of production of insulin because of the loss of pancreatic islet beta-cells because of autoimmune damage. Patients with this type of diabetes need lifelong treatment with insulin to remain alive. Poor diabetic control which predisposes to a variety of complications is not uncommon in patients treated with insulin alone. Therefore, the use of medications that can possibly enhance the therapeutic effect of insulin and reduce the risk of diabetic complications has been considered. Oral anti-diabetics including acarbose, an inhibitor of intestinal α-glucosidase, metformin, a biguanide, sulfonylureas including glipizide, and sitagliptin, an inhibitor of dipeptidyl peptidase 4 (DPP-4) are primarily used for the treatment of non-insulin dependent diabetes (Type 2). The aim of this paper is to provide an overview of the use of oral anti-diabetics in the treatment of insulin dependent diabetes (Type 1). Expert opinion: The current evidence-based expert opinion recommends the judicious use of oral anti-diabetics especially acarbose and metformin in the treatment of unsatisfactorily controlled insulin dependent diabetes type 1. These medications can help in improving diabetic control through reducing glucose levels after meals, and can contribute to lowering the levels of glycosylated hemoglobin (HbA1c). The use of these oral anti-diabetics can also help in reducing insulin requirement.

Functional Ginger-Derived Extracellular Vesicles-Coated ZIF-8 Containing TNF-α siRNA for Ulcerative Colitis Therapy by Modulating Gut Microbiota.

Tumor necrosis factor-α (TNF-α) plays a causal role in the pathogenesis of ulcerative colitis (UC), and anti-TNF-α siRNA shows great promise in UC therapy. However, delivering siRNA with site-targeted stability and therapeutic efficacy is still challenging due to the complex and dynamic intestinal microenvironment. Here, based on the functional plant-derived ginger extracellular vesicles (EVs) and porous ZIF-8 nanoparticles, we propose a novel TNF-α siRNA delivery strategy (EVs@ZIF-8@siRNA) for UC targeted therapy. Ginger EVs show strong colon and macrophage targeting, as well as robust resistance to acidic degradation in the stomach. Moreover, 6-shogaol in ginger-derived EVs displays anti-inflammatory effects, which enhance the treatment efficiency by cooperation with TNF-α siRNA. In vitro experiments reveal that ZIF-8 nanoparticles have high TNF-α siRNA loading capacity and promote siRNA escape from cellular lysosomes. In vivo experiments show that the TNF-α level is reduced more significantly in colonic tissue than other nontargeted inflammation related factors, showing a good targeting of this composite nanoparticle. Furthermore, gut microbiota sequencing results demonstrate that the nanoparticles can promote intestinal barrier repair by regulating the intestinal microbial balance and restoring the intestinal health of UC mice. Therefore, the developed EVs@ZIF-8@siRNA nanoparticles may represent a novel colon-targeted oral drug, providing a promising therapeutic strategy for UC therapy.

Medication Burden and Adverse Cardiovascular Events and Death in Patients Treated with Maintenance Hemodialysis

Key Points A higher medication burden was associated with a higher risk of adverse events in patients receiving maintenance hemodialysis.Medication burden can serve as a clinically relevant risk indicator for cardiovascular events and all-cause death in patients on maintenance hemodialysis. Background A high medication burden is associated with adverse outcomes. Although patients with ESKD have a substantial medication burden, the relationship between the number of medications in use and clinical outcomes in these patients remains unclear. Hence, this study aimed to investigate the prognostic implications of medication burden regarding adverse outcomes in patients with ESKD on maintenance hemodialysis. Methods We analyzed 29,690 patients receiving maintenance hemodialysis who participated in the Periodic Hemodialysis Quality Assessment conducted by the Health Insurance Review and Assessment Service. The exposure of interest was the number of routinely prescribed oral medications. The main outcome was a composite of nonfatal cardiovascular events (nonfatal myocardial infarction, coronary revascularization, nonfatal stroke, or hospitalization for heart failure) or all-cause death (major adverse cardiac and cerebrovascular events [MACCEs]). The secondary outcomes were the individual components of the primary outcome. Results During a follow-up period of 146,749 person-years (median, 6.0 years), MACCEs occurred in 17,573 patients (59.2%). Higher medication burden was associated with progressively higher incidence of MACCEs (84.7, 107.2, 130.2, and 168.9 events per 1000 person-years in Q1–Q4, respectively). In a multivariable Cox proportional hazard model, the adjusted hazard ratios (95% confidence intervals) for the second, third, and highest quartiles were 1.05 (1.00 to 1.10), 1.12 (1.07 to 1.17), and 1.27 (1.21 to 1.33), respectively, compared with the lowest quartile. In continuous modeling, each increase in the number of medication was associated with a 1.03-fold (95% confidence interval, 1.03 to 1.04) higher risk of the primary outcome. Conclusion A high medication burden was independently associated with higher risk of adverse cardiovascular outcomes and all-cause death in patients receiving maintenance hemodialysis. These findings suggest that a high medication burden could be a useful indicator of adverse clinical outcomes in patients undergoing hemodialysis.

A Randomized Crossover Study Comparing the Effects of Diabetes-Specific Formula with Common Asian Breakfasts on Glycemic Control and Satiety in Adults with Type 2 Diabetes Mellitus

Postprandial hyperglycemia was shown to be an independent risk factor for microvascular and macrovascular complications in type 2 diabetes mellitus (T2D). We aimed to investigate the glucose, insulin, and subjective appetite at 0, 15, 30, 45, 60, 90, 120, 150, and 180 min of three treatments: diabetes-specific formula (DSF), noodle soup, and glutinous rice. This was a randomized, crossover study with a one-week interval between treatments. Sixty-four T2D adults with oral glucose-lowering medication and HbA1c between 7% and <10% were randomized. The glucose positive area under the curve from 0 to 180 min (pAUC) was significantly lower with DSF than with glutinous rice (LSM ± SE: DSF 354 ± 32 vs. glutinous rice 451 ± 32 mmol.min/L, p = 0.033). The insulin pAUC was significantly lower with DSF (median [IQR]: 2733 [1542, 4204]) compared to glutinous rice (3359 [2193, 4744] µIU.min/mL), p = 0.042). The insulinogenic index at 30 min was significantly higher in DSF (median [IQR], 8.1 [4.2, 19.7]) compared to glutinous rice (5.4 [2.7, 11.7], p < 0.001). No significant differences were found in subjective appetite between the three treatments (all, p ≥ 0.827). There were also no significant differences in hunger, fullness, desire to eat, and prospective consumption ratings between DSF and the other two breakfasts (all p ≥ 0.181). Noodle soup led to the shortest time for hunger to return to baseline (165 min), 21 min earlier than DSF (186 min) and 32 min earlier than glutinous rice (197 min). DSF significantly reduced postprandial glucose and insulin responses compared with glutinous rice and had a higher satiating value than noodle soup in T2D adults. Replacing common Asian breakfasts with DSF may improve glycemia and hunger control.

In situ Single-Pass Perfused Rabbit Intestinal Study sample Analysis of Ractopamine by UPLC

In recent years, the prediction of oral drug absorption in humans has been a challenge for researchers and many techniques for permeability studies have been developed for several purposes, including biowaiver processes. The Single-Pass Intestinal Perfusion (SPIP) method performed in rats can provide permeability results closest to in vivo condition. he use of SPIP in rats and calculations for absorption prediction in humans may indicate the transport mechanisms and/or pre-systemic metabolism involved on permeation processes of drugs, since this model is the closest to in vivo conditions. Ractopamine hydrochloride is a commercial beta-adrenergic agonist commonly used as a dietary supplement in cattle production for improved feed efficiency and growth promotion. Currently, regulatory target tissues (as approved in the New Animal Drug Application with Food and Drug Administration) for ractopamine residue testing are muscle and liver. The aim of the study is to develop and validate an UPLC assay method to determine whether detectable and quantifiable levels of perfused ractopamine in small intestine of cattle or not. The separation is carried on Acquity UPLC BEH C18 (150mm x 2.1mm, 1.7 µm) reversed phase column using acetonitrile and 0.01M ammonium formate as the mobile phase in gradient mode at flow rate of 0.5mL/min. The precision, accuracy, extraction recovery, matrix effect, and stability meet the requirements of the guiding principles. In order to verify the sensitivity and selectivity of the method in a real-time situation, the developed method is successfully applied to a perfusion study in small intestine of rabbit and the samples were analyzed by Empower software.

Preparation of tenofovir amibufenamide fumarate spherical particles to improve tableting performance and sticking propensity by designing a spherical crystallization process

Tenofovir amibufenamide fumarate (TMF) is the first oral drug developed in Asia for the treatment of adult patients with chronic viral hepatitis B, however, further applications are limited by poor tableting performance and high sticking propensity. In this work, the spherulitic growth process of TMF has been designed and explored with the help of molecular dynamics simulation and process analysis technologies (ATR-FTIR, FBRM and EasyViewer). The spherical particles with high bulk density, good flowability and uniform particle size distribution are prepared by a simple quenching process. More importantly, experimental results show that spherical particles have higher average tensile strength (100.8% increase), higher plastic deformability and lower amount of punch sticking (87.4% decrease in 30 tablets) compared to the commercial powder products. These contributions not only shed light on the design principle of drug spherulitic growth processes, but also provide guidance for the manufacture of high-quality tablet products.

A Review: Microneedle Drug Delivery

The various common techniques for transdermal medication delivery include hypodermic needles, topical lotions, and transdermal patches. Because the stratum corneum layer of the skin acts as a barrier for molecules, the action of most therapeutic medicines is restricted, and only a few molecules are able to penetrate and reach the location of action. A novel type of delivery technology known as micro needles aids in improving medication distribution through this channel and addressing the many issues associated with traditional formulations. Because of the problems associated with oral medication delivery methods, transdermal drug administration utilising micro needles is gaining popularity. The possibilities and uses of micro needles are discussed in this review. Micro needles of many sorts can be manufactured, including solid, dissolving, hydrogel, coated, and hollow micro needles. The fabrication process chosen is determined on the kind and material of the micro needle. This technique is now being used in a variety of sectors, including oligonucleotide distribution, vaccine administration, insulin delivery, and even cosmetics.

Probabilistic human health risk assessment of commercially supplied jar water in Gopalganj municipal area, Bangladesh

Every day, the amount of quality fresh water decreases notably due to contamination of drinking water. As a result, people use commercially supplied jar water in the southern part of Bangladesh as well as in the Gopalganj municipal area. This study aims to investigate the physicochemical parameters, trace elements, and microbial parameters for assessing human health risks from oral ingestion of these elements. This study gathered commercially supplied jar water samples from 15 companies in the Gopalganj municipal area during the post-monsoon season. Temperature, potential of hydrogen (pH), total dissolved solids (TDS), electrical conductivity (EC), and salinity showed significant variation among the samples, and the level was within the national and international standard limits. The concentrations of iron (Fe) and arsenic (As) were measured using a UV–VIS spectrophotometer and atomic absorption spectroscopy (AAS), respectively. The microbial analysis was conducted by the membrane filtration method. The study found that the water samples had an average concentration of 0.16 mg/L in terms of Fe and 0.016 mg/L in terms of As, with the mean value of As exceeding the standard limits. On the other hand, the mean Fe concentration value did not exceed the standards. Probable human health risk from heavy metal in the jar water was determined by hazard quotient (HQ), hazard index (HI), and carcinogenic risk (CR) assessments. A child (HI = 3.5914) is more vulnerable to non-carcinogenic human health risks than an adult (HI = 1.6931). Furthermore, pollution in water samples was found to pose a high carcinogenic risk, with children (CR = 1.6 × 10−3) being more vulnerable to carcinogenic risk than adults (CR = 7.5 × 10−4). In the microbial analysis, 100% of the samples exceeded the total coliform and fecal coliform standard limits, and 80% of the samples exceeded the Escherichia coli standard limits. Among the samples, 7% present high risk, around 47% present medium risk, 26% show low risk, and 20% show no risk based on the E. coli standard limits. This study did not find any samples that exceeded the extremely high limit for E. coli concentration. This study found that drinking jar water samples had inadequate quality, which may increase the risk of water-borne infections such diarrhea as well as heart disease, diabetes, and cancer. As a result, the manufacturer of drinking water in jars must carry out the essential quality control procedures, and the government should regularly monitor the procedures.

Real-life effects of pharmacological osteoporosis treatments on bone mineral density by quantitative computed tomography.

Monitoring of bone mineral density (BMD) is used to assess pharmacological osteoporosis therapy. This study examined the real-life effects of antiresorptive and osteoanabolic treatments on volumetric BMD (vBMD) of the spine by quantitative computed tomography (QCT). Patients aged ≥ 50years with a vBMD < 120mg/ml had ≥ 2 QCT. For analysis of therapy effects, the pharmacological treatment and the duration of each therapy were considered. Identical vertebrae were evaluated in all vBMD measurements for each patient. A linear mixed model with random intercepts was used to estimate the effects of pharmacological treatments on vBMD. A total of 1145 vBMD measurements from 402 patients were analyzed. Considering potential confounders such as sex, age, and prior treatment, a reduction in trabecular vBMD was estimated for oral bisphosphonates (-1.01mg/ml per year; p < 0.001), intravenous bisphosphonates (-0.93mg/ml per year; p = 0.015) and drug holiday (-1.58mg/ml per year; p < 0.001). Teriparatide was estimated to increase trabecular vBMD by 4.27mg/ml per year (p = 0.018). Patients receiving denosumab showed a statistically non-significant decrease in trabecular vBMD (-0.44mg/ml per year; p = 0.099). Compared to non-treated patients, pharmacological therapy had positive effects on trabecular vBMD (1.35mg/ml; p = 0.001, 1.43mg/ml; p = 0.004, 1.91mg/ml; p < 0.001, and 6.63mg/ml; p < 0.001 per year for oral bisphosphonates, intravenous bisphosphonates, denosumab, and teriparatide, respectively). An increase in trabecular vBMD by QCT was not detected with antiresorptive agents. Patients treated with teriparatide showed increasing trabecular vBMD. Non-treatment led to a larger decrease in trabecular vBMD than pharmacological therapy.

Worldwide CTEPH Registry: Long-Term Outcomes With Pulmonary Endarterectomy, Balloon Pulmonary Angioplasty, and Medical Therapy.

The European Chronic Thromboembolic Pulmonary Hypertension registry (CTEPH), conducted between 2007 and 2012, reported the major impact of pulmonary endarterectomy (PEA) on the long-term survival of patients with CTEPH. Since then, 2 additional treatments for inoperable CTEPH have become available: balloon pulmonary angioplasty (BPA), and an approved oral drug therapy with the guanylate cyclase stimulator riociguat. The current registry aimed to evaluate the effect of these new therapeutic approaches in a worldwide context. Participation in this international global registry included 34 centers in 20 countries. Between February 2015 and September 2016, 1009 newly diagnosed, consecutive patients were included and followed until September 2019. Overall, 605 patients (60%) underwent PEA and 185 (18%) underwent BPA; 76% of the 219 remaining patients not receiving mechanical intervention (ie, neither PEA nor BPA) were treated with pulmonary hypertension drugs. Oof patients undergoing PEA and BPA, 38% and 78% also received drugs for pulmonary hypertension, respectively. Median age at diagnosis was higher in the BPA and No PEA/BPA groups than in the PEA group: 66 and 69, respectively, versus 60 years. Pulmonary vascular resistance (PVR) was similar in all groups, with an average of 643 dynes/(s·cm-5). During an observation period (>3 years; ≤5.6 years), death was reported in 7%, 11%, and 27% of patients treated by PEA and BPA, and those receiving no mechanical intervention (P<0.001). In Kaplan-Meier analysis, 3-year survival was 94%, 92%, and 71% in the 3 groups, respectively. PEA 3-year survival improved by 5% from that observed between 2007 and 2012. There was no survival difference in patients receiving vitamin K antagonists and non-vitamin K oral anticoagulants (P=0.756). In Cox regression, reduced mortality was associated with: PEA and BPA in the global cohort; history of venous thromboembolism and lower PVR in the PEA group; lower right atrial pressure in the BPA group; and use of pulmonary hypertension drugs, oxygen therapy, and lower right atrial pressure, as well as functional class in the group receiving no mechanical intervention. This second international CTEPH registry reveals important improvement in patient survival since the introduction of BPA and an approved drug for pulmonary hypertension. The type of anticoagulation regimen did not influence survival. URL https://clinicaltrials.gov; Unique identifier: NCT02656238.

Determination of bioequivalence between generic and reference drugs using laser-induced breakdown spectroscopy

BackgroundIn vitro bioequivalence studies are strictly limited to the comparison of dissolution performance to a reference drug. These studies are performed without considering the chemical similarity between the generic and reference drug formulations. This work has focused on developing a groundbreaking method based on the laser-induced breakdown spectroscopy (LIBS) technique for the in vitro bioequivalence determination of immediate-release solid oral dosage form generic drugs and as an alternative method for establishing the biowaiver of in vivo generic drug studies. ResultsThe novel LIBS-based methodology to determine in vitro bioequivalence is fast, easy to perform, and can be carried out without the requirement of tedious and complicated sample pre-treatment, nor expensive instrumentals and reagents, almost directly on the drug samples. Furthermore, the proposed methodology demonstrated that it is enough to identify the spectrochemical similarity of the formulation between generic drugs to a reference drug through the chemometric study of their LIBS spectra, based on the determination of the differentiation and similarity factors, f1 and f2, respectively, used in the pharmaceutical industry in this purpose. After analysing their LIBS spectra, the generic drugs selected for this work have all been shown to be in vitro bioequivalent, given their f1 values of less than 15 and f2 values greater than 50, according to the technical regulations on which the American and European medicines agencies are based for the approval of registration for generic immediate-release solid oral dosage form drugs. This has been evidenced even for drugs from Class III and Class IV of the biopharmaceutical classification system, whose active principle nominal concentration is very low as 0.1 and 0.25 mg/tablet, respectively. Significancefor the first time the LIBS technique has been successfully used in an advanced application for the pharmaceutical industry. The proposed method constitutes a reliable and specialized methodology for the establishment of formulation similarity between two drugs, without the requirement of separate identification of each of their components, which is a new and potential tool to determine the in vitro bioequivalence for generic immediate-release solid oral dosage form drugs.

Lignin Nanoparticles as pH-responsive Nanocarriers for Gastric-Irritant Oral Drug Aspirin.

Although lignin is one of the most naturally abundant biopolymers, the overall status of its utilization has long been subpar. The ability of Lignin to readily self-assemble into nanoparticles, along with its good biocompatibility and minimal toxicity, makes it a perfect agent for nanocarriers and drug delivery. Hence, in this study, we have attempted to examine lignin nanoparticles (LNPs) as an efficient pH-responsive nanocarrier for gastric-irritant oral NSAID, aspirin. Alkali lignin (AL) was extracted from rice straw via alkaline treatment, and the lignin nanoparticles were synthesized from lignin using the acid precipitation method. The average particle size was 201.37 ± 1.20 nm, and the synthesized LNPs exhibited a spherical shape and smooth outer surface along with high polydispersity (PDI= 0.284 ± 0.012). The LNPs showed moderate hemocompatibility during in vitro hemolysis studies. The nanoparticles presented nearly similar chemical structures to the AL from which they were developed, and the FT-IR absorption spectra confirmed the similarity of this chemical structure to the LNPs and AL. Aspirin was successfully loaded into the LNPs with a satisfactory drug loading value of 39.12 ± 1.50 and an excellent encapsulation efficiency value of 91.44 ± 0.59. Finally, the LNPs were capable of protecting the loaded drug at the acidic pH of the stomach (1.2) with just 29.20% release of the loaded aspirin after 10 h of observation in vitro. Contrarily, the LNPs were capable of rapidly releasing the aspirin at the basic pH of the intestine (7.4) with nearly 90% release of the loaded drug after 10 h observation in vitro. The basic pH of the intestine might lead to gradual dissociation of the LNPs followed by swift release of the loaded cargo. These findings substantiate that the LNPs carry the potential to be an apt and safe nanocarrier for oral drugs like aspirin as well as parenteral drugs, and LNPs can be utilized as an efficient alternative to enteric coating.

A CASE REPORT ON PARKINSON’S DISEASE (KAMPAVATA) – AN AYURVEDIC APPROACH

Parkinson's disease is a progressive neurodegenerative disease. It holds the second place among the most common diseases. The patient, in this case, report has presented with complaints of slowness of walking, difficulty in speech, tremors during activities, difficulty standing, initiating walking and getting up from a chair without support, and uncontrollable movements while walking. Through careful history taking, examination and assessment using the UPDRS scale, the patient was diagnosed with Parkinson's disease (Kampavata). She was given oral medications at OPD and then Panchakarma therapies like Rookshana, Snehanam and Brimhanam, along with oral medications for 22 days at IPD. The patient got marked improvement in her signs and symptoms. So, by this case study, it can be concluded that ayurvedic management effectively improves the quality of life of patients with Parkinson's disease.

Optimizing Dermal Delivery of Linezolid for Treating Skin and Soft Tissue Infections: NLC-Based Gel Formulation Using Taguchi Design

Background: Uncomplicated skin and soft tissue infections account for approximately 200 million visits to ambulatory care settings annually. Linezolid (LNZ) is an oxazolidinone that has proven its effectiveness in combating skin and soft tissue infections caused by gram-positive pathogens. LNZ is administered via oral suspension, tablets, or an intravenous route in most in-stances. However, its extended therapy leads to undesirable side effects like diarrhoea, thrombo-cytopenia, myelosuppression, lactic acidosis, etc. and even life-threatening complications. The dermal administration of LNZ offers an alternative route, ensuring localized and sustained release at the site of infection. This approach may reduce systemic exposure and allow for lower doses compared to oral ingestion, which can decrease the risk of adverse effects. Objective: This research aimed to develop a nanostructured lipid carrier (NLC)-based gel for de-livering LNZ via the dermal route to treat uncomplicated skin and soft tissue infections. Methods: NLC were developed by high-shear homogenisation and sonication method using glyc-eryl trimyristate as a solid lipid and neem oil as a liquid lipid. The Taguchi design was employed to optimize NLCs using surfactant concentration (mg), drug-to-lipid ratio, and sonication time (sec) as independent variables. Their effect on particle size, zeta potential, and entrapment effi-ciency was studied. The optimized nanocarriers were developed into a gel product and evaluated for drug release, permeation, and antibacterial activity. Results: The optimised process parameters to attain outcomes were 2% surfactant, 1:1 drug-to-lipid ratio and 300 seconds of sonication. The resulting NLC had an average size of 191.2 ± 2.76 nm, a zeta potential of -30.7 ± 4.50 mV, and 84.89 ± 2.76% drug entrapment. NLC-based gel dis-played anomalous transport with a 90.16 % drug release. The gel showed a strong antibacterial effect against Staphylococcus aureus with a 7.57 ± 0.12 cm mean zone of inhibition. Ex-vivo skin permeation studies revealed 24.19 ± 0.19 % drug permeation and 64.46 ± 0.58% cutaneous depo-sition. NLC-based gel demonstrated a significant decrease in colony-forming units in infected an-imal models. Conclusion: The ex-vivo investigations demonstrated the presence of LNZ at the infection site, enhancing therapeutic effectiveness. In vitro and in-vivo findings illustrated the substantial anti-bacterial efficacy of LNZ NLC-based gel. The adoption of NLC-based gel exhibits promising po-tential as a carrier for dermal delivery of LNZ.

A Perspective on the Permeability of Cocrystals/Organic Salts of Oral Drugs.

According to the BCS classification system, the differentiation of drugs is based on two essential parameters of solubility and permeability, meaning the latter is as pivotal as the former in creating marketable pharmaceutical products. Nevertheless, the indispensable role of permeability in pharmaceutical cocrystal profiles has not been sufficiently cherished, which can be most probably attributed to two principal reasons. First, responsibility may be on more user-friendly in vitro measurement procedures for solubility compared to permeability, implying the permeability measurement process seems unexpectedly difficult for researchers, whereas they have a complete understanding of solubility concepts and experiments. Besides, it may be ascribed to the undeniable attraction of introducing new crystal-based structures which mostly leaves the importance of improving the function of existing multicomponents behind. Bringing in new crystalline entities, to rephrase it, researchers have a fairly better chance of achieving high-class publications. Although the Food and Drug Administration (FDA) has provided a golden opportunity for pharmaceutical cocrystals to straightforwardly enter the market by simply considering them as derivatives of the existing active pharmaceutical ingredients, inattention to assessing and scaling up permeability which is intimately linked with solubility has resulted in limited numbers of them in the global pharmaceutical market. Casting a glance at the future, it is apprehended that further development in the field of permeability of pharmaceutical cocrystals and organic salts requires a meticulous perception of achievements to date and potentials to come. Thence, this perspective scrutinizes the pathway of permeation assessment making researchers confront their fear upfront through mapping the simplest way of permeability measurement for multicomponents of oral drugs.

Analysis of assisted reproductive outcomes in patients with atypical endometrial hyperplasia and early-stage endometrial cancer after fertility-sparing treatment.

To explore the assisted reproductive outcomes of patients with atypical endometrial hyperplasia (AEH) and early-stage endometrial cancer (EEC) who achieved complete remission after conservative treatment and to provide reference for clinical selection of appropriate conservative treatment. This retrospective cohort study included seven patients with EEC and 62 patients with AEH who underwent invitro fertilization or intracytoplasmic sperm injection at the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University between August 2015 and October 2023. The authors divided the participants into two groups based on the type of fertility-sparing treatment received: the oral medication group and the levonorgestrel-releasing intrauterine system (LNG-IUS) group. The primary outcome was the cumulative clinical pregnancy rate. Secondary outcomes included clinical pregnancy rate per transfer cycle, embryo utilization rate, and high-quality embryo rate. The LNG-IUS group had a significantly higher rate of usable embryos compared with the oral medication group (80.8% vs 91.1%, P = 0.005) and also had a thinner endometrial thickness on the day of embryo transfer. The cumulative clinical pregnancy rate was higher in the LNG-IUS group compared with the medication group (46.7% vs 78.9%, P = 0.037), and the difference was statistically significant. For patients with AEH and EEC with fertility needs, the conservative treatment method of LNG-IUS can achieve better assisted reproductive outcomes.

New topical combinations in acne therapy

Introduction. Therapeutic treatment modalities for acne involve both topical and oral medications. Fixed-dose combinations that affect all components of the pathogenesis of acne vulgaris are given preference among topical medications.Aim. To evaluate the efficacy and tolerability of Metrogyl® a topical drug, containing adapalene and metronidazole, which is used as topical therapy in patients with mild to moderate acne.Materials and methods. A prospective, open-label, randomized, single-centre comparative study was conducted in 2022. A total of 60 patients were subjected to the Mir-O-Med clinic-based observation (Krasnodar): 19 men and 41 women aged 18 to 45 years with mild to moderate acne. Group 1 received a fixed-dose combination of adapalene 1.0 mg and metronidazole10.0 mg (Metrogyl® A); Group 2 – a fixed-dose combination of adapalene 0.1% and clindomycin phosphate 1%; Group 3 – a fixed-dose combination of adapalene 0.1% and benzoyl peroxide 2.5% gel; Group 4 – adapalene 0.1%. Group 5, a separately created group, included patients from Group 1, who continued therapy for another 3 months.Results. After therapy, 6 (40%) patients from Group 1 archived clinical remission, and 9 (60%) patients found significant improvement. No deterioration in patients’ condition or absence of clinical effects was observed during therapy. The combination of adapalene and metronidazole (Metrogyl® A) to treat mild to moderate acne is comparable in terms of efficacy to the combination of adapalene and benzoyl peroxide, 10% more efficient than topical adapalene therapy and 30% more efficient than topical antibiotics combination.Conclusion. The obtained results showed high therapeutic efficacy, good tolerability and safety of Metrogyl® A, which allows to use it as monotherapy and as part of combination with other agents in patients with mild to moderate acne.

Combination of S-1 and the oral ATR inhibitor ceralasertib is effective against pancreatic cancer cells.

In our previous study, we found that the Chk1 inhibitor prexasertib enhances the antitumour effect of the oral anticancer drug S-1 against pancreatic cancer cells. In this study, we investigated the effect of combining S-1 and ceralasertib, an oral inhibitor of ATR, which is located upstream of Chk1. Ceralasertib is currently being investigated in multiple clinical trials for various cancers. The cell-proliferation inhibitory effect was measured by MTT assay, using the pancreatic cancer cell lines BxPC-3, SUIT-2, PANC-1, and MIA PaCa-2, while apoptosis was measured by flow cytometry using PI/Annexin staining. The mechanism underlying the combined effect was analysed using western blotting, and the antitumor effect was analysed using a mouse xenograft model. MTT assay revealed that the combination of S-1 and ceralasertib had a synergistic effect, leading to the suppression of cell proliferation. Measurement with PI/Annexin staining revealed that the combination of S-1 and ceralasertib induced apoptosis more efficiently than either drug alone. Western blotting results showed that ceralasertib inhibited S-1-induced activation of ATR and Chk1. The average estimated tumour volume after 3weeks of administration was 601 mm3 in the S-1 group, 580 mm3 in the ceralasertib group, and 298 mm3 in the combination group. The combination of S-1 and ceralasertib demonstrated a high antiproliferative effect in inhibiting tumour growth in vitro.

Expert consensus on the clinical application of oral small-molecule antiviral drugs against COVID-19

Abstract Although COVID‑19 no longer constitutes a “public health emergency of international concern”, which still has being spreading around the world at a low level. Small molecule drugs are the main antiviral treatment for novel coronavirus recommended in China. Although a variety of small‑molecule antiviral drugs against COVID‑19 have been listed in China, there is no specific drug recommendation for special populations. Society of Bacterial Infection and Resistance of Chinese Medical Association, together with the National Clinical Research Center for Respiratory Disease, and the National Center for Respiratory Medicine, organized domestic experts in various fields such as respiratory, virology, infection, critical care, emergency medicine and pharmacy to release Expert Consensus on the Clinical Application of Oral Small‑Molecule Antiviral Drugs against COVID‑19. The main content of this consensus includes the introduction of seven small‑molecule antiviral drugs against COVID‑19, focusing on the drug recommendations for 14 special groups such as the elderly, patients with complicated chronic diseases, tumor patients, pregnant women, and children, and providing suggestions for clinicians to standardize drug use. Practice guideline registration: International Practice Guideline Registration for Transparency (PREPARE-2023CN617)

Therapeutic Advances in Psoriasis: From Biologics to Emerging Oral Small Molecules.

Psoriasis is a persistent, inflammatory condition affecting millions globally, marked by excessive keratinocyte proliferation, immune cell infiltration, and widespread inflammation. Over the years, therapeutic approaches have developed significantly, shifting from conventional topical treatments and phototherapy to more sophisticated systemic interventions such as biologics and, recently, oral small-molecule drugs. This review seeks to present a comprehensive investigation of the existing psoriasis treatment options, focusing on biologic agents, oral small molecules, and emerging treatments. Several categories of biologic treatments have received regulatory approval for psoriasis, including TNF-α, IL-17, IL-12/23, and IL-23 inhibitors. Biologics have revolutionized the treatment of psoriasis. These targeted therapies offer significant improvement in disease control and quality of life, with acceptable safety profiles. However, limitations such as cost, potential immunogenicity, and administration challenges have driven the exploration of alternative treatment modalities. Oral small molecules, particularly inhibitors of Janus kinase (JAK), have emerged as options due to their convenience and efficacy. These agents represent a paradigm shift in the management of the condition, offering oral administration and targeted action on specific signaling pathways. In addition to existing therapies, the review explores emerging treatments that hold promise for the future of psoriasis care. These include innovative small-molecule inhibitors. Early-stage clinical trials suggest these agents may enhance outcomes for psoriasis patients. In conclusion, the therapeutic landscape of psoriasis is rapidly evolving, emphasizing targeted, patient-centered treatments. Ongoing research and development are expected to lead to more personalized and effective management strategies for this complex condition.