Biguanides and lactic acidosis:unraveling the complex relationship

Biguanides,such as metformin,have long been established as frontline medications for the management of type 2 diabetes due to their glucose-lowering effects and favorable safety profiles.However,concerns regarding the risk of lactic acidosis associated with biguanide use have sparked considerable debate and scrutiny.This research article aims to provide a comprehensive analysis of the relationship between biguanides,particularly metformin,and lactic acidosis.We delve into the underlying mechanisms,epidemiological evidence,risk factors,clinical manifestations,diagnostic considerations,and management strategies related to biguanide-induced lactic acidosis.Additionally,we explore recent research developments,controversies,and future directions in this critical area of pharmacovigilance and clinical practice.

Metformin-associated lactic acidosis:A mini review of pathophysiology,diagnosis and management in critically ill patients

Metformin is a common diabetes drug that may reduce lactate clearance by inhibiting mitochondrial oxidative phosphorylation,leading to metforminassociated lactic acidosis(MALA).As diabetes mellitus is a common chronic metabolic condition found in critically ill patients,pre-existing metformin use can often be found in critically ill patients admitted to the intensive care unit or the high dependency unit.The aim of this narrative mini review is therefore to update clinicians about MALA,and to provide a practical approach to its diagnosis and treatment.MALA in critically ill patients may be suspected in a patient who has received metformin and who has a high anion gap metabolic acidosis,and confirmed when lactate exceeds 5 mmol/L.Risk factors include those that reduce renal elimination of metformin(renal impairment from any cause,histamine-2 receptor antagonists,ribociclib)and excessive alcohol consumption(as ethanol oxidation consumes nicotinamide adenine dinucleotides that are also required for lactate metabolism).Treatment of MALA involves immediate cessation of metformin,supportive management,treating other concurrent causes of lactic acidosis like sepsis,and treating any coexisting diabetic ketoacidosis.Severe MALA requires extracorporeal removal of metformin with either intermittent hemodialysis or continuous kidney replacement therapy.The optimal time to restart metformin has not been well-studied.It is nonetheless reasonable to first ensure that lactic acidosis has resolved,and then recheck the kidney function post-recovery from critical illness,ensuring that the estimated glomerular filtration rate is 30 mL/min/1.73 m^(2) or better before restarting metformin.

Clinical effects of antidiabetic drugs on psoriasis:The perspective of evidence-based medicine

Psoriasis and diabetes shared common underlying pathophysiological mechanisms.Emerging data suggested that antidiabetic medications may improve the psoriasis severity in patients with diabetes mellitus.Several hypoglycemic agents including thiazolidinediones,glucagon-like peptide-1 receptor agonists,dipeptidyl peptidase-4 inhibitors,and biguanides have been reported to make a remarkable reduction in the Psoriasis Area and Severity Index score from baseline.This antipsoriatic effect could be mediated not only by the glucoselowering action of these agents but also via inhibition of keratinocyte over proliferation,increase expression of differentiation markers,suppression the immune inflammatory pathway,and blocking the calcium channels and mitogen-activated protein kinase signaling pathways.On the other hand,there was no significant increase in adverse reactions associated with the treatment of pioglitazone or metformin.However,previous studies often had the relatively short duration of the trials,and did not have enough power to assess recurrence of psoriasis.Potential bias in the study and missing data could undermine the reliability of the results.Therefore,the appropriately randomized controlled studies with large sample sizes and long-term durations in various psoriasis patients are warranted for further support.

Cost-Effectiveness Analysis of Oral Hypoglycemics for Type-2 Diabetes Mellitus at a Tertiary Care Hospital, Nepal

An observational follow-up study on 63 newly diagnosed Type-Ⅱ diabetic patients was conducted at Tribhuvan University Teaching Hospital, a tertiary care centre, Kathmandu, Nepal. The aims of the study were to determine demographics, prescribing patterns, drug costs and to analyze the effectiveness of different hypoglycemic therapies. The effectiveness of glucose control was analyzed by Wilcoxon signed rank test. The majority of patients (31%) fell into the age strata of 50-60 years. A total of 63 prescriptions were screened including anti-diabetics drugs and other drugs. The average number of drugs per prescription sheet was 2.72 ± 2.23. Eighty-two percent (82%) of the patients were recommended oral hypoglycemic agents. The prescribing frequency of biguanides was more than sulphonylureas. Biguanides were prescribed more frequently than sulfonylureas. The biguanide monotherapy group (p = 0.001) and the combination of biguanide and sulfonylureas (p = 0.028) were the most effective treatment methods, and the p-value of fasting blood glucose was the lowest at follow-up. Nearly 55% of patients receiving the combination achieved glucose control. In summary, this study reflects the best treatment for patients with diabetes. Future studies of larger patient populations need to evaluate existing treatment models to ensure good practice and quality of care.

Rapid,simple and stability-indicating determination of polyhexamethylene biguanide in liquid and gel-like dosage forms by liquid chromatography with diode-array detection

A rapid and simple method for the determination of potyhexamethylene biguanide （polyhexanide, PHMB） in liquid and gel-like pharmaceutical formulations by means of high performance liquid chromatography coupled to diode-array detection （HPLC DAD） was devel- oped. Best separation was achieved using a cyanopropyl bonded phase （Agilent Zorbax Eclipse XDB-CN column 4.6mm x 75 mm with particle size of 3.5 μm） as well as gradient elution consisting of acetonitrile/deionized water at a flow rate of 1.0 mL/min. The optimized and applied chromatographic conditions permitted separation of polyhexanide from interacting raatrix with subsequent detection at a wavelength of 235 nm with good sensitivity. The method validation was carried out with regard to the guidelines for analytical procedures demanded by the International Conference on Harmonisation （ICH）. Mean recoveries of 102% and 101% for gel-like as well as liquid preparations were obtained. Suitable repeatability as well as intermediate precision could bc achieved with limits of detection ≤0.004 mg/mL for both formulations, equivalent to ≤0.004% PHMB concerning sample preparation. Determination of PHMB was accomplished without tedious sample preparation. Interacting matrix could be eliminated by the chromatographicprocedure with excellent performance of system suitability. All analytical requirements were fulfilled permitting a reliable and precise determination of PHMB in pharmaceuticals. Further- more, the developed method was applied to stability testing of pharmaceutical preparations containing PHMB.

The Antimicrobial Activity of Wool Fabrics Treated with Crosslinking Agents and Polyhexamethylene Biguanide

In this study,we used citric acid(CA)as a crosslinking agent,mixed with polyhexamethylene biguanide,to perform a pad-dry-cure treatment on wool fabrics to study its antimicrobial effects and physical properties.

Novel Elastomeric Fabrics for the Treatment of Hypertrophic Burn Scars Using Polyhexamethylene Biguanide Antimicrobial Agents

In burn treatments,microorganisms on pressure garments during pressure therapy can prevent rehabilitation by causing functional,hygienic,and aesthetic difficulties. As bacterium is one of the most trouble-causing organisms,they can threaten patients causing infection during the long period of use of these garments.Novel burn pressure garments having durable antimicrobial property were developed using polyhexamethylene biguanide( PHMB)antimicrobial agent procedure on highly elastic nylon 66 /spandex fabrics in powernet,flat warp and weft knitted structures using paddry-cure method. Commercial wireless pressure sensors were used to control pressures at an acceptable medical range. Antimicrobial activity,wash durability,Fourier transform infrared spectroscopy(FTIR) and Scanning electron microscopy(SEM) analyses were conducted for the treated samples. Antimicrobial test results following AATCC 100 Test Method showed 99% reduction of bacteria for the fabric samples treated with PHMB. A small but significant decrease in antimicrobial activity was observed even after50 launderings. These treatments also yield good results to prevent odor,decrease infection by preventing and /or blocking microbial growth according to the antimicrobial mechanism and support reducing of scarring by providing a hygienic environment around the scar.

Polyhexamethylene Biguanide in Vaginal Solution Is Effective in the Treatment of Vulvovaginal Candidiasis: A Pilot Study

Vaginitis is one of the most recurrent conditions that afflict women and require medical care. Vulvovaginal candidiasis (VVC) is frequently related to vaginal carriage of Candida albicans, an opportunistic polymorphic fungus, which colonizes the human skin, the mucosa and the reproductive tract. Actually, standard treatments to counteract vaginitis include several topical and oral treatments. The aim of this study was to evaluate the efficacy of a new biguanide compound, polyhexamethylene biguanide (PHMB) in avaginal solution, in women affected by vaginal candidiasis. For this reason, 40 women showing the symptoms previously ascribed to vaginal candidiasis were recruited and treated with a single PHMB dose of vaginal solution. After a single dose of treatment, 80% of them had a complete resolution of the fungal infection;furthermore, all of them reported clinical benefits, statistically significant reduction in both clinical signs and symptoms of candidiasis and a score’s reduction of 50%.

Clinical impact of an anti-biofilm Hydrofiber dressing in hard-to-heal wounds previously managed with traditional antimicrobial products and systemic antibiotics

Background:Hard-to-heal wounds are often compromised by the presence of biofilm.This presents an infection risk,yet traditional antimicrobial wound care products and systemic antibiotics are often used despite the uncertainty of therapeutic success and wound progression.The aim of this study was to investigate the clinical impact of a next-generation anti-biofilm Hydrofiber wound dressing(AQUACEL Ag+Extra[AQAg+E])in hard-to-heal wounds that had previously been treated unsuccessfully with traditional silver-,iodine-or polyhexamethylene biguanide(PHMB)-containing dressings and products and/or systemic antibiotics.Methods:Clinical case study evaluations of the anti-biofilm dressing were conducted,where deteriorating or stagnant wounds were selected by clinicians and primary dressings were replaced by the anti-biofilm dressing for up to 4 weeks,or as deemed clinically appropriate,with monitoring via case report forms.The data was stratified for cases where traditional silver-,iodine-or PHMBcontaining products,or systemic antibiotics,had been used prior to the introduction of the antibiofilm dressing.Results:Sixty-five cases were identified for inclusion,wounds ranging in duration from 1 week to 20 years(median:12 months).In 47(72%)cases the wounds were stagnant,while 15(23%)were deteriorating;3 wounds were not recorded.After an average of 4.2 weeks of management with the anti-biofilm dressing(range:1–11 weeks),in 11(17%)cases the wounds had healed(i.e.complete wound closure),40(62%)wounds improved,9(14%)wounds remained the same and 5(8%)wounds deteriorated.Conclusions:The introduction of this anti-biofilm dressing into protocols of care that had previously involved wound management with traditional antimicrobial products and/or antibiotics was shown to facilitate improvements in the healing status of most of these hard-to-heal wounds.Dressings containing proven anti-biofilm technology,in combination with antimicrobial silver and exudate management technology,appear to be an effective alternative to traditional antimicrobial products and antibiotics in the cases presented here.The use of antimicrobial wound dressings that contain anti-biofilm technology may have a key role to play in more effective wound management and antibiotic stewardship.

Multiple Hydrogen Bond-Induced Structural Distortion for Broadband White-Light Emission in Two-Dimensional Perovskites

Low-dimensional hybrid lead-halide perovskites with broadband white-light emission upon near-UV excitation have attracted immense scientific interest due to their potential application for the next generation of solid-state lighting as well as scintillators for radiation detection.Recently,broadband emission material is mostly reported in structural distorted perovskites.However,it is still unclear how to generate structural distortion in low-dimensional perovskites.