Recent Developments in 1,2,3-Triazole based α-Glucosidase Inhibitors: Design Strategies, Structure-activity Relationship and Mechanistic Insights.

Diabetes mellitus is a chronic and most prevalent metabolic disorder affecting 422 million the people worldwide and causing life-threatening associated conditions including disorders of kidney, heart, and nervous system as well as leg amputation and retinopathy. Steadily rising cases from the last few decades suggest the failure of currently available drugs in containment of this disease. α-Glucosidase is a potential target for effectively tackling this disease and attracting significant interest from medicinal chemists around the globe. Besides having a set of side effects, currently available α-glucosidase inhibitors (carbohydrate mimics) offer better tolerability, safety, and synergistic pharmacological outcomes with other antidiabetic drugs therefore medicinal chemists have working extensively over last three decades for developing alternative α-glucosidase inhibitors. The 1,2,3-Triazole nucleus is energetically used by various research groups around the globe for the development of α-glucosidase inhibitors posing it as an optimum scaffold in the field of antidiabetic drug development. This review is a systematic analysis of α-glucosidase inhibitors developed by employing 1,2,3-triazole scaffold with special focus on design strategies, structure-activity relationships, and mechanism of inhibitory effect. This article will act as lantern for medicinal chemists in developing of potent, safer, and effective α-glucosidase inhibitors with desired properties and improved therapeutic efficacy.

Coumarin as an Elite Scaffold in Anti-Breast Cancer Drug Development: Design Strategies, Mechanistic Insights, and Structure-Activity Relationships.

Breast cancer is the most common cancer among women. Currently, it poses a significant threat to the healthcare system due to the emerging resistance and toxicity of available drug candidates in clinical practice, thus generating an urgent need for the development of new potent and safer anti-breast cancer drug candidates. Coumarin (chromone-2-one) is an elite ring system widely distributed among natural products and possesses a broad range of pharmacological properties. The unique distribution and pharmacological efficacy of coumarins attract natural product hunters, resulting in the identification of numerous natural coumarins from different natural sources in the last three decades, especially those with anti-breast cancer properties. Inspired by this, numerous synthetic derivatives based on coumarins have been developed by medicinal chemists all around the globe, showing promising anti-breast cancer efficacy. This review is primarily focused on the development of coumarin-inspired anti-breast cancer agents in the last three decades, especially highlighting design strategies, mechanistic insights, and their structure-activity relationship. Natural coumarins having anti-breast cancer efficacy are also briefly highlighted. This review will act as a guideline for researchers and medicinal chemists in designing optimum coumarin-based potent and safer anti-breast cancer agents.

The development of thymol-isatin hybrids as broad-spectrum antibacterial agents with potent anti-MRSA activity.

Bacterial resistance toward available therapeutic agents has become a nightmare for the healthcare system, causing significant mortality as well as prolonged hospitalization, thereby needing the urgent attention of research groups working on antimicrobial drug development worldwide. Molecular hybridization is a well-established tool for developing multifunctional compounds to tackle drug resistance. Inspired by the antibacterial profiles of isatin and thymol, along with the efficiency of a triazole linker in molecular hybridization, herein, we report the design, synthesis and antibacterial activity of a novel series of triazole tethered thymol-isatin hybrids. Most of the hybrids exhibited a broad-spectrum antibacterial efficacy against standard human pathogenic as well as clinically isolated multidrug-resistant bacterial strains listed in the WHO's 'priority pathogen' list and also in the ESKAPE group. Among them, hybrid compound AS8 was the most effective against methicillin-resistant Staphylococcus aureus (MIC = 1.9 µM and MBC = 3.9 µM), exhibiting biofilm inhibitory potential. AS8 exhibited dehydrosqualene synthase (CrtM) inhibitory potential in MRSA and decreased the production of virulence factor staphyloxanthin, which is one of the key mechanisms of its anti-MRSA efficacy, which was further supported by molecular docking and simulation studies. Moreover, AS8 was found to be non-toxic and showed a potent in vivo antibacterial efficacy (90% survival at 10 mg kg-1) as well as a modulated immune response in the larva-based (Galleria mellonella) model of systemic infections. Overall findings confirmed that AS8 can be a promising candidate or take the lead in the treatment and further drug development against drug-resistant infectious diseases, especially against MRSA infections.

Past, present and future of xanthine oxidase inhibitors: design strategies, structural and pharmacological insights, patents and clinical trials.

Xanthine oxidase, a molybdo-flavoenzyme, and an isoform of xanthine dehydrogenase both exist as xanthine oxidoreductase and are responsible for purine catabolism. Xanthine oxidase is more involved in pathological conditions when extensively modulated. Elevation of xanthine oxidase is not only the prime cause of gout but is also responsible for various hyperuricemia associated pathological conditions like diabetes, chronic wounds, cardiovascular disorders, Alzheimer's disease, etc. Currently available xanthine oxidase inhibitors in clinical practice (allopurinol, febuxostat and topiroxostat) suffer from fatal side effects that pose a serious problem to the healthcare system, raising global emergency to develop novel, potent and safer xanthine oxidase inhibitors. This review will provide key and systematic information about: a. design strategies (inspired from both marketed drugs in clinical practice and natural products), structural insights and pharmacological output (xanthine oxidase inhibition and associated activities) of various pre-clinical candidates reported by various research groups across the globe in the past two decades; b. patented xanthine oxidase inhibitors published in the last three decades and c. clinical trials and their outcomes on approved drug candidates. Information generated in this review has suggested fragment-based drug design (FBDD) and molecular hybridization techniques to be most suitable for development of desired xanthine oxidase inhibitors as one provides high selectivity toward the enzyme and the other imparts multifunctional properties to the structure and both may possess capabilities to surpass the limitations of currently available clinical drugs. All in combination will exclusively update researchers working on xanthine oxidase inhibitors and allied areas and potentially help in designing rational, novel, potent and safer xanthine oxidase inhibitors that can effectively tackle xanthine oxidase related disease conditions and disorders.

Recent Updates in Inhalable Drug Delivery System against Various Pulmonary Diseases: Challenges and Future Perspectives.

In the current scenario, pulmonary disease has become a prime burden for morbidity and mortality alongside tremendous social and economic crises throughout the world. Numerous conventional drug delivery system and treatment approach targeting the respiratory region has been driven out. However, effective and accurate recovery has not been achieved yet. In this regard, nanotechnological-based inhalable drug delivery strategy including polymeric, lipidic, or metallic-based respirable microparticles plays an indispensable role in circumventing numerous challenges faced during traditional treatment. Excellent aerodynamic performance leads to enhanced lung targetability, reduced dosing frequency and hence systemic toxicities, as well as improved pharmaceutical attributes, and therefore pharmacokinetic profiles are interminable factors associated with nanotechnologicalbased inhalable delivery. In this review, we comprehensively explored recent advancements in nanotechnologically engineered inhalable formulations targeting each of the mentioned pulmonary diseases. Moreover, we systematically discussed possible respiratory or systemic toxicities about the indeterminate and undefined physicochemical characteristics of inhaled particles.

Pathogenesis of Alzheimer's Disease and Diversity of 1,2,3-Triazole Scaffold in Drug Development: Design Strategies, Structural Insights, and Therapeutic Potential.

Alzheimer's disease is a most prevalent form of dementia all around the globe and currently poses a significant challenge to the healthcare system. Currently available drugs only slow the progression of this disease rather than provide proper containment. Identification of multiple targets responsible for this disease in the last three decades established it as a multifactorial neurodegenerative disorder that needs novel multifunctional agents for its management and the possible reason for the failure of currently available single target clinical drugs. 1,2,3-Triazole is a miraculous nucleus in medicinal chemistry and the first choice for development of multifunctional hybrid molecules. Apart from that, it is an integral component of various drugs in clinical trials as well as in clinical practice. This review is focused on the pathogenesis of Alzheimer's disease and 1,2,3-triazole containing derivatives developed in recent decades as potential anti-Alzheimer's agents. The review will provide (A) precise insight of various established targets of Alzheimer's disease including cholinergic, amyloid, tau, monoamine oxidases, glutamate, calcium, and reactive oxygen species hypothesis and (B) design hypothesis, structure-activity relationships, and pharmacological outcomes of 1,2,3-triazole containing multifunctional anti-Alzheimer's agents. This review will provide a baseline for various research groups working on Alzheimer's drug development in designing potent, safer, and effective multifunctional anti-Alzheimer's candidates of the future.

Mechanistic insight and structure activity relationship of isatin-based derivatives in development of anti-breast cancer agents.

Breast cancer is most common in women and most difficult to manage that causes highest mortality and morbidity among all diseases and posing significant threat to mankind as well as burden on healthcare system. In 2020, 2.3 million women were diagnosed with breast cancer and it was responsible for 685,000 deaths globally, suggesting the severity of this disease. Apart from that, relapsing of cases and resistance among available anticancer drugs along with associated side effects making the situation even worse. Therefore, it is a global emergency to develop potent and safer antibreast cancer agents. Isatin is most versatile and flying one nucleus which is an integral competent and various anticancer agent in clinical practice and widely used by various research groups around the globe for development of novel, potent, and safer antibreast cancer agents. This review will shed light on the structural insights and antiproliferative potential of various isatin-based derivatives developed for targeting breast cancer in last three decades that will help researchers in design and development of novel, potent, and safer isatin-based antibreast cancer agents.

Recent advances in antifungal drug development targeting lanosterol 14α-demethylase (CYP51): A comprehensive review with structural and molecular insights.

Fungal infections are posing serious threat to healthcare system due to emerging resistance among available antifungal agents. Among available antifungal agents in clinical practice, azoles (diazole, 1,2,4-triazole and tetrazole) remained most effective and widely prescribed antifungal agents. Now their associated side effects and emerging resistance pattern raised a need of new and potent antifungal agents. Lanosterol 14α-demethylase (CYP51) is responsible for the oxidative removal of 14α-methyl group of sterol precursors lanosterol and 24(28)-methylene-24,25-dihydrolanosterol in ergosterol biosynthesis hence an essential component of fungal life cycle and prominent target for antifungal drug development. This review will shed light on various azole- as well as non-azoles-based derivatives as potential antifungal agents that target fungal CYP51. Review will provide deep insight about structure activity relationship, pharmacological outcomes, and interactions of derivatives with CYP51 at molecular level. It will help medicinal chemists working on antifungal development in designing more rational, potent, and safer antifungal agents by targeting fungal CYP51 for tackling emerging antifungal drug resistance.

1,2,3-Triazole Derivatives as an Emerging Scaffold for Antifungal Drug Development against Candida albicans: A Comprehensive Review.

Candida infections are most prominent among fungal infections majorly target immunocompromised and hospitalized patients and cause significant morbidity and mortality. Candida albicans is the notorious and most prevalent among all pathogenic Candida strains. Its emerging resistance toward available antifungal agents making it hard to tackle and emerging as global healthcare emergency. Simultaneously, 1,2,3-triazole nucleus is a privileged scaffold that is gaining importance in antifungal drug development due to being a prominent bioactive linker and isostere of triazole based antifungal class core 1,2,4-triazole. Numerous reports have been updated in scientific literature in last few decades related to utilization of 1,2,3-triazole nucleus in antifungal drug development against Candida albicans. Present review will shed light on various preclinical studies focused on development of 1,2,3-triazole derivatives targeting Candida albicans along with brief highlight on clinical trials and newly approved drugs. Structure-activity relationship has been precisely discussed for each architect along with future perspective that will help medicinal chemists in design and development of potent antifungal agents for tackling infections derived from Candida albicans.

Role of sodium dependent SLC13 transporter inhibitors in various metabolic disorders.

The sodium dependent SLC13 family transporters comprise of five genes SLC13A1, SLC13A2 (NaDC1), SLC13A3 (NaDC3), SLC13A4 and SLC13A5 (NaCT). Among them, NaDC1, NaDC3 and NaCT are sodium dependent transporters belonging to family of dicarboxylates (succinate, malate, α-ketoglutarate) and tricarboxylates (citrate). The mouse and the human NaCT structures have still not been crystallized, therefore structural information is taken from the related bacterial transporter of VcINDY. Citrate in the cytosol works as a precursor for the fatty acid synthesis, cholesterol, and low-density lipoproteins. The excess citrate from the matrix is translocated to the cytosol for fatty acid synthesis through these transporters and thus controls the energy balance by downregulating the glycolysis, tricarboxylic acid (TCA), and fatty acid breakdown. These transporters play an important role in regulating various metabolic diseases including cancer, diabetes, obesity, fatty liver diseases and CNS disorders. These di and tricarboxylate transporters are emerging as new targets for metabolic disorders such as obesity and diabetes. The mutation in the function of the NaCT causes several neurological diseases including neonatal epilepsy and impaired brain development whereas mutation of genes coding for citrate transport present in the liver may provide positive effect. Therefore, continued efforts from the earlier work on citrate transporters are required for the development of citrate inhibitors. This review discusses the structure, function, and regulation of the NaCT transporter. The review also highlights citrate role in diagnosing diseases such as cancer, diabetes, fatty liver, and diabetes. The therapeutic perspective of synthetic inhibitors against NaCT transporters is succinctly summarized.

Membrane Estrogen Receptor ß Is Sufficient to Mitigate Cardiac Cell Pathology.

Estrogen acting through estrogen receptor ß (ERß) has been shown to oppose the stimulation of cardiac myocytes and cardiac fibroblasts that results in cardiac hypertrophy and fibrosis. Previous work has implicated signal transduction from ERß as being important to the function of estrogen in this regard. Here we address whether membrane ERß is sufficient to oppose key mechanisms by which angiotensin II (AngII) stimulates cardiac cell pathology. To do this we first defined essential structural elements within ERß that are necessary for membrane or nuclear localization in cells. We previously determined that cysteine 418 is the site of palmitoylation of ERß that is required and sufficient for cell membrane localization in mice and is the same site in humans. Here we determined in Chinese hamster ovarian (CHO) cells, and mouse and rat myocytes and cardiac fibroblasts, the effect on multiple aspects of signal transduction by expressing wild-type (WT ) or a C418A-mutant ERß. To test the importance of the nuclear receptor, we determined a 4-amino acid deletion in the E domain of ERß that strongly blocked nuclear localization. Using these tools, we expressed WT and mutant ERß constructs into cardiomyocytes and cardiac fibroblasts from ERß-deleted mice. We determined the ability of estrogen to mitigate cell pathology stimulated by AngII and whether the membrane ERß is necessary and sufficient.

Update on the Management of Brain Metastasis.

Brain metastases occur in almost one-third of adult patients with solid tumor malignancies and lead to considerable patient morbidity and mortality. The rising incidence of brain metastases has been ascribed to the development of better imaging and screening techniques and the formulation of better systemic therapies. Until recently, the multimodal management of brain metastases focused primarily on the utilization of neurosurgical techniques, with varying combinations of whole-brain radiation therapy and stereotactic radio-surgical procedures. Over the past 2 decades, in particular, the increment in knowledge pertaining to molecular genetics and the pathogenesis of brain metastases has led to significant developments in targeted therapies and immunotherapies. This review article highlights the recent updates in the management of brain metastases with an emphasis on novel systemic therapies.

A statistical method to optimize the chemical etching process of zinc oxide thin films.

Zinc oxide (ZnO) is an attractive material for microscale and nanoscale devices. Its desirable semiconductor, piezoelectric and optical properties make it useful in applications ranging from microphones to missile warning systems to biometric sensors. This work introduces a demonstration of blending statistics and chemical etching of thin films to identify the dominant factors and interaction between factors, and develop statistically enhanced models on etch rate and selectivity of c-axis-oriented nanocrystalline ZnO thin films. Over other mineral acids, ammonium chloride (NH4Cl) solutions have commonly been used to wet etch microscale ZnO devices because of their controllable etch rate and near-linear behaviour. Etchant concentration and temperature were found to have a significant effect on etch rate. Moreover, this is the first demonstration that has identified multi-factor interactions between temperature and concentration, and between temperature and agitation. A linear model was developed relating etch rate and its variance against these significant factors and multi-factor interactions. An average selectivity of 73 : 1 was measured with none of the experimental factors having a significant effect on the selectivity. This statistical study captures the significant variance observed by other researchers. Furthermore, it enables statistically enhanced microfabrication processes for other materials.

Nipecotic acid as potential lead molecule for the development of GABA uptake inhibitors; structural insights and design strategies.

Gamma-Aminobutyric Acid (GABA) inhibitory neurotransmitter departs an energetic role in brain signalling system. Levels of GABA in the brain influence human behaviour, diminishes in the degree of GABA can cause seizures, depression, Parkinson's. To put it plainly, it plays a basic part in the significant issues of mind. It is exceptionally important to cure the issues linked to GABA. Writing overview proposed that nipecotic acid is an intense GABA reuptake inhibitor. This scaffold is likewise present in one of the promoted anticonvulsant drugs 'Tiagabine'. Tiagabine is only drug in the market which works through this mechanism however the medication is regulated with one more prescription for the synergistic impact. Nipecotic acid has several disadvantages such as it can't cross the blood-brain barrier because of its hydrophilic and zwitterionic nature. To avoid this problem nipecotic acid scaffold hybrids with the different aromatic groups can enhance the physical (lipophilicity) as well as biological properties of the resultant compound. So, there is a dire requirement for compounds that work through this mechanism. Several medicinal chemists and researchers are already working in this field and developed outstanding newer molecules. This review article compiles these developed new hybrids along with design strategies, structure-activity relationship, and biological activity as well as in silico studies. This review also demonstrates the synthesis of nipecotic acid and the core mechanism through which nipecotic acid acts as a GABA reuptake inhibitor.

Overview of Chemistry and Therapeutic Potential of Non-Nitrogen Heterocyclics as Anticonvulsant Agents.

Epilepsy is a chronic neurological disorder, characterized by the predisposition of unprovoked seizures affecting the neurobiological, psychological, cognitive, economic, and social wellbeing of the patient. As per the 2019 report by World Health Organization, it affects nearly 80% of the population, which comes from middle to low-income countries. It has been suggested that 70% of such cases can be treated effectively if properly diagnosed. It is one of the most common neurological diseases affecting 50 million people globally. Most of the antiepileptic drugs used in clinical practice are only 60-80% effective in controlling the disease. These drugs suffer from serious drawbacks of non-selectivity and toxicity that limit their clinical usefulness. Hence, there is a need to search for safe, potent, and effective anti-epileptic drugs. One of the emerging strategies to discover and develop selective and non-toxic anticonvulsant molecules focuses on the design of non-nitrogen heterocyclic compounds (NNHC). Drugs such as valproic acid, gabapentin, viagabatrin, fluorofelbamate, tiagabine, progabide, pregabalin, gamma amino butyric acid (GABA), etc. do not contain a nitrogen heterocyclic ring but are as effective anticonvulsants as conventional heterocyclic nitrogen compounds. This review covers the various classes of NNHC which have been developed in the recent past as anticonvulsants along with their chemistry, percentage yield, structure-activity relationship and biological activity. The most potent compound in each series has been identified for comparative studies, for further structural modification and to improve the pharmacokinetic profile. Various optimized synthetic pathways and diverse functionalities other than nitrogen-containing rings discussed in the article may help medicinal chemists to design safe and effective anticonvulsant drugs in near future.

Design Strategies, Chemistry and Therapeutic Insights of Multi-target Directed Ligands as Antidepressant Agents.

Depression is one of the major disorders of the central nervous system worldwide and causes disability and functional impairment. According to the World Health Organization, around 265 million people worldwide are affected by depression. Currently marketed antidepressant drugs take weeks or even months to show anticipated clinical efficacy but remain ineffective in treating suicidal thoughts and cognitive impairment. Due to the multifactorial complexity of the disease, single-target drugs do not always produce satisfactory results and lack the desired level of therapeutic efficacy. Recent literature reports have revealed improved therapeutic potential of multi-target directed ligands due to their synergistic potency and better safety. Medicinal chemists have gone to great extents to design multitarget ligands by generating structural hybrids of different key pharmacophores with improved binding affinities and potency towards different receptors or enzymes. This article has compiled the design strategies of recently published multi-target directed ligands as antidepressant agents. Their biological evaluation, structural-activity relationships, mechanistic and in silico studies have also been described. This article will prove to be highly useful for the researchers to design and develop multi-target ligands as antidepressants with high potency and therapeutic efficacy.

Reactive metabolites of the anticonvulsant drugs and approaches to minimize the adverse drug reaction.

Several generations of antiepileptic drugs (AEDs) are available in the market for the treatment of seizures, but these are amalgamated with acute to chronic side effects. The most common side effects of AEDs are dose-related, but some are idiosyncratic adverse drug reactions (ADRs) that transpire due to the formation of reactive metabolite (RM) after the bioactivation process. Because of the adverse reactions patients usually discontinue the medication in between the treatment. The AEDs such as valproic acid, lamotrigine, phenytoin etc., can be categorized under such types because they form the RM which may prevail with life-threatening adverse effects or immune-mediated reactions. Hepatotoxicity, teratogenicity, cutaneous hypersensitivity, dizziness, addiction, serum sickness reaction, renal calculi, metabolic acidosis are associated with the metabolites of drugs such as arene oxide, N-desmethyldiazepam, 2-(1-hydroxyethyl)-2-methylsuccinimide, 2-(sulphamoy1acetyl)-phenol, E-2-en-VPA and 4-en-VPA and carbamazepine-10,11-epoxide, etc. The major toxicities are associated with the moieties that are either capable of forming RM or the functional groups may itself be too reactive prior to the metabolism. These functional groups or fragment structures are typically known as structural alerts or toxicophores. Therefore, minimizing the bioactivation potential of lead structures in the early phases of drug discovery by a modification to low-risk drug molecules is a priority for the pharmaceutical companies. Additionally, excellent potency and pharmacokinetic (PK) behaviour help in ensuring that appropriate (low dose) candidate drugs progress into the development phase. The current review discusses about RMs in the anticonvulsant drugs along with their mechanism vis-a-vis research efforts that have been taken to minimize the toxic effects of AEDs therapy.

Chondrosarcoma of Mandible: A Rare Case Report.

INTRODUCTION: Chondrosarcomas (CS) are malignant mesenchymal tumours with cartilaginous differentiation that rarely affects the maxillofacial region. It accounts for approximately 10-20% of malignant bone tumours. The CS is rare in occurrence with aggressive course with high malignant potential, and poor prognosis. CASE REPORT: Here we report a rare case of a 37year old female presenting tumoral mass in the lower jaw, for the past 3 years, which was gradually progressive in nature with an area of skin ulceration. The CT revealed a well- defined lesion with soft tissue component measuring 15x12x10 cm in size infiltrating both right and left masseter. Biopsy confirmed the diagnosis of grade IIICS. Considering the size and aggressive nature of the lesion, surgical resection was done. The reconstruction of the mandible was done with vascularised fibula pedicle flap to achieve acceptable cosmesis. The patient was discharged uneventfully. Though few cases of high grade CS have been reported in literature but CS of this enormous size has not been reported yet. CONCLUSION: In this case report we documented the management of a relatively rare but challenging reconstructive maxillofacial surgery. Since in this case the CS was enormous in size and aggressive surgery was required, the cosmetic and functional outcomes were challenging. In our case report we have found that a vascularised fibula pedicle flap gives a good functional and cosmetic outcome and can be used for reconstruction of complete mandible.

Brain natriuretic peptide in pregnant women with heart disease.

BACKGROUND: Plasma brain natriuretic peptide levels were prospectively studied in pregnant women with heart disease. METHODS: Fifty pregnant women with heart disease and 25 controls were evaluated at 24 weeks or under, 30-32 weeks, 34 weeks or more of gestation, and 6 weeks postpartum. Adverse maternal cardiac events were hospitalization for worsening heart failure, stroke, and death. RESULTS: Thirty-eight (76%) women had rheumatic heart disease. Plasma brain natriuretic peptide levels were (in cases and controls) 118.3 ± 46.5 pg/ml and 66.3 ± 15.9 pg/ml (at 24 weeks or under), 124.8 ± 30.4 pg/ml and 68.4 ± 16.5 pg/ml (30-32 weeks), 135.8 ± 34.9 pg/ml and 68.6 ± 15.6 pg/ml (34 weeks or more), and 110.1 ± 21.9 pg/ml and 65.0 ± 16.1 pg/ml (6 weeks postpartum) (p = .0001). Eighteen women had adverse events. Of these, only 1 had a level less than 100 pg/ml, 12 were between 100 and 200 pg/ml, and 5 more than 200 pg/ml. CONCLUSIONS: Plasma brain natriuretic peptide levels were higher in women with heart disease at all periods of gestation as well as six weeks postpartum. No woman with a plasma brain natriuretic peptide levels of 98 pg/ml or less had an adverse event.

The performance of high-volume bronchoalveolar lavage for the evaluation and diagnosis of interstitial lung disease.

Although high-volume bronchoalveolar lavage (BAL) is an excellent research tool, its use in the evaluation of interstitial lung disease remains controversial, particularly in the age of lung biopsy in video-assisted thoracic surgery. Recently, a new practice guideline made several important recommendations for the performance of the procedure and the handling, processing, and analysis of samples. Here we describe this recommended technique, our experience performing BAL in 42 patients, and the usefulness of our differential cell count results. We demonstrate that BAL is straightforward and safe to perform and conclude that it may offer valuable data in evaluating interstitial lung disease, particularly in patients with an acute presentation or who are not fit for lung biopsy.