Different Mechanisms Of Action Research Articles

Insulin-sensitizing agents for infertility treatment in woman with polycystic ovary syndrome: a narrative review of current clinical practice.

Polycystic ovary syndrome (PCOS) is an endocrine, metabolic, and reproductive disorder which, according to the Rotterdam criteria, affects up to 24% of women of childbearing age. Although the prevalence of infertility in this subpopulation of women is high, the optimal treatment has not been fully established yet. Insulin resistance is considered to be an important mechanism involved in the development of PCOS; hence, the aim of this narrative review is to present an overview of the current pharmacological insulin-sensitizing treatment modalities for infertile women with PCOS. A MEDLINE and PubMed search for the years 1990-2023 was performed using a combination of keywords. Clinical trials with insulin sensitizers used for infertility treatment as well as analyses of systematic reviews and meta-analyses were evaluated. When deemed necessary, additional articles referenced in the retrieved papers were included in this narrative review. Several insulin-sensitizing compounds and various therapeutical protocols are available for infertility treatment of women with PCOS. Metformin is the most common adjuvant medication to induce ovulation in infertile women with PCOS and is more frequently administered in combination with clomiphene citrate than on its own. Recently, inositol and glucagon-like peptide-1 (GLP-1) receptor agonists have emerged as possible options for infertility treatment in PCOS. The future of medical treatment of PCOS women with infertility lies in a personalized pharmacological approach, which involves various compounds with different mechanisms of action that could modify ovarian function and endometrial receptivity, ultimately leading to better overall reproductive outcomes in these women.

The immune response of Locusta migratoria manilensis at different times of infection with Paranosema locustae.

Paranosema locustae is an entomopathogenic microsporidia with promising potential for controlling agricultural pests, including Locusta migratoria manilensis. However, it has the disadvantage of having a slow insecticidal rate, and how P. locustae infection impacts the host immune response is currently unknown. The present study investigated the effect of P. locustae on the natural immune response of L. migratoria and the activities of enzymes that protect against oxidative stress. Infection with P. locustae increased the hemocytes and nodulation number of L. migratoria at the initial stage of infection. The hemocyte-mediated modulation of immune response was also affected by a decrease in the number of hemocytes 12 days postinfection. Superoxide dismutase activity in locusts increased in the early stages of infection but decreased in the later stages, whereas the activities of peroxidase (POD) and catalase (CAT) showed opposite trends may be due to their different mechanisms of action. Furthermore, the transcription levels of mRNA of antimicrobial peptide-related genes and phenoloxidase activity in hemolymph in L. migratoria were suppressed within 15 days of P. locustae infection. Overall, our data suggest that P. locustae create a conducive environment for its own proliferation in the host by disrupting the immune defense against it. These findings provide useful information for the potential application of P. locustae as a biocontrol agent.

The evolution of multiple sclerosis disease-modifying therapies: An update for pharmacists.

Multiple sclerosis (MS) and the evolution of disease-modifying therapies (DMTs) and their indications, mechanisms of action, efficacy, pregnancy class, and cost are discussed. MS is an immune-mediated, demyelinating, and progressive neurological disorder that can cause both motor and cognitive deficits. Onset of MS typically occurs between the ages of 20 and 40 years, and the disease can result in significant disability over time. Since the introduction of the first DMT for the treatment of MS in 1993, significant progress has been made in the development of new classes of DMTs with different mechanisms of action, higher efficacy, and simpler administration schedules, offering patients better alternatives. However, drawbacks with the use of DMTs include their increasing cost and formulary restrictions. The treatment landscape of MS has significantly changed over the past 2 decades, and the introduction of newer classes of DMTs provides an opportunity for pharmacists to play an important role in the management of this patient population.

Medical therapy for conjunctivitis. Literature review

Conjunctivitis, according to various studies, is the most common reason for going to the initial outpatient appointment and can be caused by several factors at the same time. Treatment is carried out comprehensively, depending on the clinical picture, somatic status and anamnesis data. In accordance with the clinical guidelines developed by the Russian Association of Ophthalmologists, the following groups of drugs are recommended for use: antibacterial, antiseptic, antihistamine, nonsteroidal anti-inflammatory drugs.Purpose: to analyze the use of the above groups of drugs in the treatment of conjunctivitis in order to recommend a reasonable prescription of the necessary therapy.Materials and methods. The literature data on the study of the features of the action of the above pharmacological groups in the treatment of conjunctivitis, obtained on the resources of PubMed, eLibrary, Crossref Metadata, mainly over the past 20 years, are presented.Results. The presence of signs of an allergic reaction involves the appointment of antiallergic drugs with multiple pharmacological effects – blockade of histamine receptors, stabilization of mast cell membranes and suppression of eosinophil filtration. Given the different mechanisms of action within this group of drugs, it is necessary to select them individually. When prescribing tablet forms of antihistamines, it must be remembered that with prolonged use, they can cause patients to feel dry in their eyes. In cases where the above antiallergic drugs do not adequately control the allergic inflammatory process, anti-inflammatory drugs are used. Nonsteroidal and steroid anti-inflammatory drugs are used as anti-inflammatory drugs. Usually nonsteroidal anti-inflammatory drugs are recommended for use in chronic conjunctivitis and patients with a history of systemic diseases. Steroid drugs are indicated for severe forms of manifestation of the allergic process on the eyes, as well as the appointment of steroid anti-inflammatory drugs is recommended for use in short courses (up to 2 weeks), and with their longer use, control of intraocular pressure is necessary. Literature data indicate the lack of efficacy of antiviral drugs such as acyclovir and others from this group in the treatment of conjunctivitis of adenoviral etiology. Drugs with an immunomodulatory effect based on interferon or inducers of interferon synthesis are widely used. The prescription of antibiotics should be justified, since in recent years the level of resistance to them has significantly increased. Antiseptics that have a wide spectrum of action (bacteria, viruses, fungi and protozoa) are an alternative to antibiotics, but it must be remembered that this group of drugs often causes allergic reactions.Conclusion. The treatment of conjunctivitis must be approached carefully, taking into account not only the etiology of the disease, but also the somatic and immune status of the patient. To avoid the negative effects of the use of antibiotics, replace them with alternative drugs and do not use them in the treatment of conjunctivitis of a non-bacterial nature.

PCSK9 Antagonists: Clinical Efficacy and Main Trends in the Development of New Medicines

Scientific relevance. Cardiovascular diseases (CVD) are the leading cause of death worldwide. Dyslipidemia, as the pathophysiological basis of atherosclerosis, is the most important cause of CVD. Among the factors that modify this pathology, the World Health Organisation lists statins, which effectively reduce the cholesterol level. However, statin treatment compliance is not sufficient to achieve population-based lipid targets. This is a powerful stimulus for the creation of fundamentally new groups of lipid-lowering agents, in particular, antagonists of proprotein convertase subtilisin/kexin type 9 (PCSK9).Aim. The study aimed to review innovative approaches to developing a new generation of lipid-lowering agents, PCSK9 antagonists, and to evaluate the effectiveness, safety, and clinical potential of these medicines.Discussion. PCSK9 antagonists significantly increase the effectiveness of lipid-lowering therapy when combined with statins and are an effective monotherapy in patients with contraindications for statins. PCSK9 monoclonal antibodies, as well as inclisiran, have a favourable risk–benefit ratio. However, the high cost of commercially available PCSK9 antagonists limits their clinical use. A number of promising directions exist for developing new PCSK9 antagonists that have fundamentally different mechanisms of action, such as adnectins; genome editing with CRISPR/Cas9; combining small molecules with low molecular weight PCSK9 inhibitors; PCSK9 vaccines; and antisense oligonucleotides. Medicinal products from these groups are currently at various stages of preclinical and clinical development.Conclusions. Therefore, new lipid-lowering agents can be developed by synthesising high and low molecular weight PCSK9 ligands and by altering the genetic mechanisms of PCSK9 synthesis. The innovative medicines considered in this review are highly effective, and most have shown no signs of toxicity at the pre-authorisation stage.

Divergence in Glyphosate Susceptibility between Steinchisma laxum Populations Involves a Pro106Ser Mutation.

The characterization of the mechanisms conferring resistance to herbicides in weeds is essential for developing effective management programs. This study was focused on characterizing the resistance level and the main mechanisms that confer resistance to glyphosate in a resistant (R) Steinchisma laxum population collected in a Colombian rice field in 2020. The R population exhibited 11.2 times higher resistance compared to a susceptible (S) population. Non-target site resistance (NTSR) mechanisms that reduced absorption and impaired translocation and glyphosate metabolism were not involved in the resistance to glyphosate in the R population. Evaluating the target site resistance mechanisms by means of enzymatic activity assays and EPSPS (5-enolpyruvylshikimate-3-phosphate synthase) gene sequencing, the mutation Pro106Ser was found in R plants of S. laxum. These findings are crucial for managing the spread of S. laxum resistance in Colombia. To effectively control S. laxum in the future, it is imperative that farmers use herbicides with different mechanisms of action in addition to glyphosate and adopt Integrate Management Programs to control weeds in rice fields of the central valleys of Colombia.

Antiepileptic Drugs and the Relationship with the Intestinal Microbiota

This review of the literature examines the use of antiepileptic medications and how they relate to gut microbiota. Relationships exist between the makeup of the intestinal microbiota and the development and execution of the most fundamental physiological processes. Additionally, it affects the functioning of the central nervous system (CNS) by interacting with the microbiota-intestine-brain axis. The use of pharmaceutical medication is one of the factors that can alter the composition of the gut microbiota. When treating epilepsy, various drug types are used, each with a different mechanism of action. Among the medications in question are to piramate, primidone, phenytoin, carbamazepine, and phenobarbital. The similarity in structure and function between enteric and nerve cells establishes the connection between the brain and the gut. Valproic acid significantly reduced intestinal inflammation in research involving rats with colitis. Its limited ability to treat seizures in these circumstances may be due to the enterocytes limited ability to absorb this medicine. The study came to the conclusion that colitis patients and people with healthy gut, brain, and microbiota interactions typically respond better to antiepileptics and anticonvulsants than people with imbalances in this axis. These imbalances can result in a lower seizure threshold and an increased frequency of epileptic seizures.

Rational Design of Novel Peptidomimetics against Influenza A Virus: Biological and Computational Studies.

Effective therapy against the influenza virus is still an unmet goal. Drugs with antiviral effects exist, but the appearance of resistant viruses pushes towards the discovery of drugs with different mechanisms of action. New anti-influenza molecules should target a good candidate, as a new anti-influenza molecule could be an inhibitor of the influenza A virus hemagglutinin (HA), which plays a key role during the early phases of infection. In previous work, we identified two tetrapeptide sequences, SLDC (1) and SKHS (2), derived from bovine lactoferrin (bLf) C-lobe fragment 418-429, which were able to bind HA and inhibit cell infection at picomolar concentration. Considering the above, the aim of this study was to synthesize a new library of peptidomimetics active against the influenza virus. In order to test their ability to bind HA, we carried out a preliminary screening using biophysical assays such as surface plasmon resonance (SPR) and orthogonal immobilization-free microscale thermophoresis (MST). Biological and computational studies on the most interesting compounds were carried out. The methods applied allowed for the identification of a N-methyl peptide, S(N-Me)LDC, which, through high affinity binding of influenza virus hemagglutinin, was able to inhibit virus-induced hemagglutination and cell infection at picomolar concentration. This small sequence, with high activity, represents a good starting point for the design of new peptidomimetics and small molecules.

Multimodal analgesia regime for open spine fixation surgery: A case series

Postoperative pain is a common and significant problem that affects millions of patients worldwide. Inadequate pain control can lead to a range of negative outcomes, including prolonged hospital stays, delayed recovery, increased healthcare costs, and decreased patient satisfaction. Therefore, effective management of postoperative pain is essential for improving patient outcomes and reducing healthcare utilization. While progress has been made in improving postoperative pain management, there are still significant gaps in our understanding of the mechanisms underlying postoperative pain and the most effective interventions for its management. Further research is needed to optimize pain management strategies and reduce the burden of postoperative pain on patients and healthcare systems.Multimodal analgesia is an approach to pain management that uses a combination of medications and other interventions to effectively manage pain while minimizing side effects. The goal is to target pain at different points in the pain pathway, using different mechanisms of action, to achieve better pain control than could be achieved with a single medication alone. By using multiple medications that work through different mechanisms, a lower dose of each medication can be used, reducing the risk of side effects. The approach is often tailored to the individual patient, taking into account their medical history, the type of surgery or injury, and their level of pain. Overall, multimodal analgesia aims to improve pain control and patient outcomes while reducing the risk of adverse effects.

Current Status of Angiogenesis Inhibitors as Second-Line Treatment for Unresectable Colorectal Cancer.

Colorectal cancer is the third most common disease and the second most common cause of death around the world. The drug for second-line treatment depends on the drugs used in first-line treatment and the biomarker status. As biomarkers, the RAS gene, BRAF gene, and dMMR/MSI-H, TMB-H, and HER2 statuses have been established in clinical practice, and the corresponding molecularly targeted therapeutic agents are selected based on the biomarker status. Given the frequency of biomarkers, it is assumed that when patients move on to second-line treatment, an angiogenesis inhibitor is selected in many cases. For second-line treatment, three angiogenesis inhibitors, bevacizumab (BEV), ramucirumab (RAM), and aflibercept (AFL), are available, and one of them is combined with cytotoxic agents. These three angiogenesis inhibitors are known to inhibit angiogenesis through different mechanisms of action. Although no useful biomarkers have been established for the selection of angiogenesis inhibitors, previous biomarker studies have suggested that angiogenesis-related factors such as VEGF-A and VEGF-D might be predictors of the therapeutic efficacy of angiogenesis inhibitors. These biomarkers are measured as protein levels in plasma and are considered to be promising biomarkers. We consider that the rationale for selecting among these three angiogenesis inhibitors should be clarified to benefit patients.

Efficacy of Biologics in Patients with Allergic Severe Asthma, Overall and by Blood Eosinophil Count: A Literature Review.

Patients with uncontrolled, allergic severe asthma may be prescribed biologic therapies to reduce exacerbations and improve disease control. Randomized controlled trials (RCTs) of these therapies have differed in design, with varying results overall and by baseline blood eosinophil count (BEC). This study describes published annualized asthma exacerbation rate (AAER) reductions from RCTs in patients with allergic severe asthma, overall and by baseline BEC category. A literature search was performed to identify published phase 3 RCT data of US Food and Drug Administration-approved biologics for severe asthma in patients with severe, uncontrolled asthma and confirmed sensitization to perennial aeroallergens. Analyses focused on AAER reduction versus placebo in the overall population and/or in those with an elevated or low BEC at baseline or screening. Baseline serum total immunoglobulin E levels varied between RCT populations. In patients with allergic severe asthma across all BEC categories, data were available for tezepelumab, dupilumab, benralizumab and omalizumab only; the greatest AAER reduction was observed with tezepelumab. In patients with allergic severe asthma and BECs of ≥ 260 cells/µL or ≥ 300 cells/μL, AAER reductions were observed with all biologics (tezepelumab, dupilumab, mepolizumab, benralizumab and omalizumab); the greatest AAER reduction was observed with tezepelumab and the smallest AAER reduction was observed with omalizumab. In patients with allergic severe asthma and BECs of < 260 cells/µL or < 300 cells/μL (regardless of historical BEC), an AAER reduction was observed with tezepelumab but not with benralizumab or omalizumab. Differential mechanisms of action may explain the differences in results observed between biologics. Among patients with allergic severe asthma, the efficacy of biologics in RCTs varied considerably overall and by BEC. Tezepelumab was the only biologic to demonstrate AAER reductions consistently across all subgroups. These differences can inform provider treatment decisions when selecting biologic treatments for patients with allergic severe asthma.

Grounded theory approach to non-market strategy and organizational resilience: the case of Chinese private enterprise

PurposeThis study aims to explore the relationship between non-market strategies and organizational resilience, using a Chinese private enterprise as an example.Design/methodology/approachThis study collected data through semi-structured interviews and analyzed them through grounded theory, using a three-step approach of open coding, axial coding and selective coding to analyze and construct a model of the mechanism of the impact of non-market strategies on organizational resilience.FindingsThe following conclusions were drawn from this study. (1) Stakeholders, internal and external environment and entrepreneurship are important motivations that influence private firms to implement non-market strategies to enhance organizational resilience, with entrepreneurship being the key driver. (2) Non-market strategies contain three dimensions, and different non-market behaviors have different mechanisms of action on the organizational resilience of firms. (3) Non-market strategies and organizational resilience form an interactive spiral relationship. This mutually reinforcing effect promotes firm growth and sustainable corporate development. The research results enrich the theoretical connotation of non-market strategies, construct a model of the mechanism of influence of non-market strategies on organizational resilience, and describe three explanatory paths for the relationship between the two–incentive mechanism, functional mechanism and transformation mechanism.Research limitations/implicationsThis study's single case is unique and based on the Chinese context. In addition, this study adopts a rooted qualitative research approach and although the coding and model construction strictly follow the steps of grounded theory research, a degree of subjectivity is inevitable. On this basis, future research can adopt quantitative analysis methods to test and improve the model.Practical implicationsThis paper explores the important role of non-market strategies in the Chinese context under the impact of traditional market mechanisms, based on the perspective of Chinese private enterprises, and provides new insights and revelations for private enterprises to achieve sustainable development.Originality/valueThis study innovatively explores the formation mechanism of organizational resilience from the perspective of non-market strategies, adding a new perspective to the literature. Additionally, it examines the mechanisms between long-term non-market strategy and organizational resilience, particularly their relationship in times of crisis, utilizing a rooted approach that goes beyond static analysis.

The Association between Immune Checkpoint Proteins and Therapy Outcomes in Acute Myeloid Leukaemia Patients.

The development of novel drugs with different mechanisms of action has dramatically changed the treatment landscape of AML patients in recent years. Considering a significant dysregulation of the immune system, inhibitors of immune checkpoint (ICI) proteins provide a substantial therapeutic option for those subjects. However, use of ICI in haematological malignancies remains very limited, in contrast to their wide use in solid tumours. Here, we analysed expression patterns of the most promising selected checkpoint-based therapeutic targets in AML patients. Peripheral blood of 72 untreated AML patients was used for flow cytometric analysis. Expression of PD-1, PD-L1, CTLA-4, and B7-H3 was assessed within CD4+ (Th) lymphocytes and CD33+ blast cells. Patients were stratified based on therapy outcome and cytogenetic molecular risk. AML non-responders (NR) showed a higher frequency of PD-1 in Th cells compared to those with complete remission (CR). Reduced blast cell level of CTLA-4 was another factor differentiating CR from NR subjects. Elevated levels of PD-1 were associated with a trend for poorer patients' survival. Additionally, prognosis for AML patients was worse in case of a higher frequency of B7-H3 in Th lymphocytes. In summary, we showed the significance of selected ICI as outcome predictors in AML management. Further, multicentre studies are required for validation of those data.

Pharmacological Therapy in Inflammatory Bowel Diseases: A Narrative Review of the Past 90 Years.

Inflammatory Bowel Diseases had their first peak in incidence in countries in North America, Europe, and Oceania and are currently experiencing a new acceleration in incidence, especially in Latin America and Asia. Despite technological advances, 90 years after the development of the first molecule for the treatment of IBD, we still do not have drugs that promote disease remission in a generalized way. We carried out a narrative review on therapeutic advances in the treatment of IBD, the mechanisms of action, and the challenges facing the therapeutic goals in the treatment of IBD. Salicylates are still used in the treatment of Ulcerative Colitis. Corticosteroids have an indication restricted to the period of therapeutic induction due to frequent adverse events, while technologies with less systemic action have been developed. Most immunomodulators showed a late onset of action, requiring a differentiated initial strategy to control the disease. New therapeutic perspectives emerged with biological therapy, initially with anti-TNF, followed by anti-integrins and anti-interleukins. Despite the different mechanisms of action, there are similarities between the general rates of effectiveness. These similar results were also evidenced in JAK inhibitors and S1p modulators, the last therapeutic classes approved for the treatment of IBD.

Molecular Background and Clinical Implications of Glucose Disorders in Patients with Psoriatic Arthritis.

Psoriatic arthritis (PsA) is an inflammatory musculoskeletal disease characterized by joint and entheses involvement. This condition is often associated with an increased prevalence of obesity, encompassing more than one-third of all patients. Given the presence of metabolic disorders, it becomes crucial to enhance clinical oversight of metabolic parameters. An early diagnosis of glucose irregularities in PsA allows for the assessment of an effective treatment strategy. The approach proves valuable in preventing the development of insulin resistance (IR) or diabetes mellitus type 2 (DMt2). Similar pathways characterize the pathomechanism of PsA and DMt2, offering an innovative perspective on treatment management. The cytokines and adipokines synthesized in the course of PsA significantly impact the development process of IR and DMt2 in different mechanisms of action. Conversely, glucose disorders influence the activity of PsA and therapy outcomes. Given the chronic inflammatory background shared by PsA, obesity, and DMt2, it is evident that inadequate management of any of the mentioned conditions can exacerbate the others. Thus, when PsA coincides with DMt2, a comprehensive multidimensional approach is necessary. This includes an effective immunosuppressive regimen complemented by appropriate anti-diabetic and insulin therapies. Moreover, often overlooked recommendations concerning overall well-being and lifestyle adjustments hold significance. This manuscript explores the connections and the relationship between the molecular background of PsA and glucose disorders. It provides a detailed exposition of specific therapeutic approaches for both conditions.

Identifying synergistic combinations of Doxorubicin-Loaded polyquercetin nanoparticles and natural Products: Implications for breast cancer therapy

Combining chemotherapeutic agents with bioactive natural products is an attractive cancer treatment modality to reduce the dose and side effects of chemotherapy. Combination treatments with drugs having different mechanisms of action can also be beneficial in combatting the development of drug resistance by cancer cells. Nanoparticle (NP)-mediated drug delivery can further improve the therapeutic index of cytotoxic agents by enabling passive and/or active targeting to tumor tissues in vivo. Using doxorubicin (DOX) as a model chemotherapeutic agent, we developed three NP formulations based on polyquercetin (pQCT), an emerging nanocarrier platform. The NPs were co-assembled with DOX, pQCT, and either Pluronic P123, methoxy poly(ethylene glycol)-amine, or D-α-tocopheryl poly(ethylene glycol) 1000 succinate (TPGS). Physicochemical characterization of the NPs revealed them to have a spherical morphology with high monodispersity, excellent drug loading capacity, and sustained drug release. Then, the NPs were evaluated in vitro to determine their potential synergism when combined with the bioactive natural products curcumin (CUR), tannic acid (TA), and thymoquinone (TQ) against breast cancer cells (MCF-7 and MDA-MB-231). Surprisingly, most of the combinations were found to be antagonistic. However, combinations containing CUR exhibited greater pro-apoptotic effects compared to the single agents, with polymer-modified pQCT NPs presenting as a promising nanoplatform for enhancing DOX’s ability to promote cancer cell apoptosis. Our findings provide insights into the potential application of pQCT in nanomedicine, as well as the use of bioactive natural products in combination with DOX as a free agent and as an NP formulation in the treatment of breast cancer.

Treating Treatment-resistant Depression with Esketamine Nasal Spray When All Therapeutic Options Have Been Exhausted: Clinical Experience from a Spanish Cohort of Expanded Use.

: Treatment Resistant Depression (TRD) is commonly defined as the lack of response to two or more anti-depressants with different mechanisms of action. Up to 30% of patients diagnosed with major depressive disorder might be considered to present TRD. The objective of this study was to assess the effectiveness and tolerability of esketamine in patients diagnosed with TRD, who were referred to our program after exhausting all available treatments. A secondary objective consisted in researching the relationship between response and previous use of electroconvulsive therapy. : A prospective, observational study was carried out in patients enrolled in the expanded use of esketamine in our center. They received esketamine prior to its marketing authorisation, for therapeutic purposes. Sixteen subjects were analyzed. Effectiveness was assessed with the Montgomery-Asberg depression rating scale (MADRS). Patients were followed up to 4 months after the administration. : Esketamine showed a rapid, robust effect in improving depressive symptoms, with no specific correlation between outcome and any demographic or clinical traits evaluated. No differences were found between patients that previously received Electroconvulsive Therapy, and those that didn't. 10 out of 16 patients responded (＞ 50% change in baseline MADRS scores), but only five achieved remission (＜ 12 points in the global MADRS score). We provide some recommendations, based on clinical experience, to improve tolerability and adherence, and to manage adverse effects. : Results suggest that esketamine is a safe, effective and rapid-acting option for TRD. More studies are needed to properly assess predictors of response outcome.

The Pivotal Role of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers in Hypertension Management and Cardiovascular and Renal Protection: A Critical Appraisal and Comparison of International Guidelines.

Arterial hypertension is the main preventable cause of premature mortality worldwide. Across Latin America, hypertension has an estimated prevalence of 25.5-52.5%, although many hypertensive patients remain untreated. Appropriate treatment, started early and continued for the remaining lifespan, significantly reduces the risk of complications and mortality. All international and most regional guidelines emphasize a central role for renin-angiotensin-aldosterone system inhibitors (RAASis) in antihypertensive treatment. The two main RAASi options are angiotensin-converting enzyme inhibitors (ACEis) and angiotensin II receptor blockers (ARBs). Although equivalent in terms of blood pressure reduction, ACEis are preferably recommended by some guidelines to manage other cardiovascular comorbidities, with ARBs considered as an alternative when ACEis are not tolerated. This review summarizes the differences between ACEis and ARBs and their place in the international guidelines. It provides a critical appraisal of the guidelines based on available evidence from randomized controlled trials (RCTs) and meta-analyses, especially considering that hypertensive patients in daily practice often have other comorbidities. The observed differences in cardiovascular and renal outcomes in RCTs may be attributed to the different mechanisms of action of ACEis and ARBs, including increased bradykinin levels, potentiated bradykinin response, and stimulated nitric oxide production with ACEis. It may therefore be appropriate to consider ACEis and ARBs as different antihypertensive drugs classes within the same RAASi group. Although guideline recommendations only differentiate between ACEis and ARBs in patients with cardiovascular comorbidities, clinical evidence suggests that ACEis provide benefits in many hypertensive patients, as well as those with other cardiovascular conditions.

Adhesive Capsulitis of the Ankle (Frozen Ankle): An Infrequent Syndrome.

Adhesive capsulitis, characterized by progressive fibrosis, causes a gradual, painful loss of both active and passive articular motion, leading to the final contracture of the joint capsule. The condition commonly referred to as "frozen ankle" (FA), which Goldman was the first to use, relates to the ankle joint and is challenging to both diagnose and treat. Data acquired from people who suffer from this type of damage in other joints such as the shoulder, hip, and wrist also exists. Despite the fact that a well-defined model for the medical management of FA does not exist, a wide spectrum of local treatments, both surgical and non-surgical, exist. This review gives an overview of the current scientific position of the frozen ankle in terms of evolutionary factors, etiology, the different mechanisms of action involved, current treatment options, and other possible interventions based on recent discoveries of pathophysiological mechanisms. The application of extracorporeal shockwave therapy, stretching exercises, and corticosteroid injections combined with physical therapy modalities that enhance pain management, range of motion, and functional capacity is highly advisable for the treatment of adhesive capsulitis, commonly known as "frozen joints". Furthermore, the addition of interventions both impacting and analyzing chronic hypoxia, low-grade inflammation, and sedentary life is proposed.

Herbicides for monochoria (Monochoria vaginalis) control in transplanted rice

AbstractIn Iran, monochoria is a noxious weed in fields of transplanted rice. Two field experiments were conducted to assess the efficacy of soil-applied and foliar-applied herbicides to control monochoria in transplanted rice. Prepackaged herbicides (triafamone plus ethoxysulfuron applied at 40 g ai ha−1, pyrazosulfuron-ethyl plus pretilachlor applied at 382.5 g ai ha−1, and pendimethalin plus clomazone applied at 1,200 g ai ha−1) reduced monochoria biomass by 100%, 100%, and 14%, respectively; and a single application of flucetosulfuron at 30 g ai ha−1, pendimethalin at 990 g ai ha−1, thiobencarb at 2,750 g ai ha−1, and pretilachlor at 1,000 g ai ha−1 reduced monochoria biomass by 100%, 99%, 75%, and 56%, respectively, compared with a nontreated control. Tank-mixed bensulfuron-methyl at 45 g ai ha−1 applied with pretilachlor, thiobencarb, or pendimethalin provided 100% control of monochoria. Rice height, and straw and grain yield were greater after herbicide treatments than those of the nontreated and hand-weeded controls, indicating the advantages of chemical control of monochoria over manual weeding. Full-season monochoria interference reduced rice grain yield by 32%. In the second study, the herbicides triafamone plus ethoxysulfuron, flucetosulfuron, 2,4-D at 1,080 g ai ha−1, dicamba plus 2,4-D at 928 g ai ha−1, bispyribac-sodium at 31.25 g ai ha−1, bentazon plus MCPA at 1,150 g ai ha−1, pyribenzoxim at 30 g ai ha−1, and propanil at 5,400 g ai ha−1 applied to foliage at 4- to 5-leaf seedlings of monochoria provided ≥97% control and prevented 100% of its regrowth, with the exception of propanil. This study shows that monochoria control can be achieved by using a variety of residual and foliar-applied herbicides with different mechanisms of action.