Proliferative Glomerulonephritis With Monoclonal IgG Deposits: Another Unusual Presentation.

Proliferative glomerulonephritis with monoclonal immunoglobulin G (IgG) deposits (PGNMID) is a relatively rare diagnosis with variable presentation. When detectable, the disease is typically indolent rather than malignant and recurs in transplant cases. Here, we report a case of PGNMID, which presented clinically as rapidly progressive glomerulonephritis (RPGN). The patient presented to his primary care physician's office with diarrhea for one day and was admitted for acute kidney injury. Urine sediment was active, and the patient had nephrotic range proteinuria. Serologic workup was negative for any monoclonality: ANA, c-ANCA, and p-ANCA. Kidney biopsy showed diffuse proliferative and crescentic glomerulonephritis with IgG3-kappa restricted deposits, consistent with PGNMID. The patient required dialysis initiation, and corticosteroids were administered. The patient declined further immunomodulatory treatment and remains hemodialysis-dependent. This case highlights the potential for severe renal damage from monoclonal proteins despite an indolent or even undetectable hematologic clone. This entity needs further studies to better understand its immuno-physiological background and develop a standard treatment regimen.

Dialyzing a Brain-Dead Individual for Organ Procurement.

Many patients are unable to receive organ transplantation as there is an expanding gap between the number of patients waiting for an organ and the number who receive it. Organ procurement from the brain-dead can address this expanding gap, especially because one brain-dead patient can potentially donate multiple organs to several recipients. Here, we describe a rare case of a previously healthy 26-year-old male who was declared brain dead after a motor vehicle accident but underwent hemodialysis to treat his acute kidney injury and hyperkalemia before successfully donating his heart and left kidney.

Universal Health Care System in India: An In-Depth Examination of the Ayushman Bharat Initiative.

This editorial provides an in-depth review of the Ayushman Bharat initiative, India's universal healthcare scheme, designed to address significant disparities in healthcare access and quality across the country. Following the structure of the healthcare system and socioeconomic trends, the manuscript assesses the reasons for the initiative's creation, its coverage, implementation strategies, role during the COVID-19 pandemic, auxiliary pilot programs, and challenges for future progress. It focuses on how the initiative has increased healthcare accessibility, financial protection, transformed the healthcare infrastructure, and provided relief during the COVID-19 crisis. Critical issues such as gaps between supply and demand, the need for increased government spending, and the challenges of access and quality in rural health centers are also discussed. We aim to raise awareness about the program's benefits among potential beneficiaries, which is a key to the initiative's success and a potential role model for equitable global healthcare.

A Rare Presentation of Narcolepsy With Cataplexy After Vaccines in a Genetically Susceptible Elderly Woman: A Case Report.

Observing cataplexy episodes during an office visit is extremely rare as they are usually triggered by laughter or emotional stress. Narcolepsy usually occurs in the younger population. We report a case of a 65-year-old Caucasian female with a past medical history of obesity who developed excessive daytime sleepiness, fatigue, and sleep attacks five weeks after getting influenza and pneumococcal vaccines. The presentation of cataplexy was atypical. Several episodes of cataplexy were observed during the office visit without any emotional trigger. Further workup, including polysomnography (PSG), was positive for obstructive sleep apnea, controlled with continuous positive airway pressure (CPAP) use. Later, she had PSG with CPAP use, which optimally controlled obstructive sleep apnea, followed by multiple sleep latency tests (MSLT) with CPAP use. It was positive for narcolepsy with a mean sleep latency of 1.6 minutes with sleep onset rapid eye movement (REM) in five out of five naps. Her cerebrospinal fluid (CSF) hypocretin level was extremely low at 50 pg/ml, usually seen in narcolepsy with cataplexy. She was also positive for human leukocyte antigen (HLA) DBQ1*06:02. The diagnosis of narcolepsy with cataplexy was made, which improved with medications for narcolepsy.

Morphological, chemical and molecular characterization of Centella asiatica germplasms for commercial cultivation in the Indo-Gangetic plains.

Centella asiatica germplasm collected from north, north-eastern and southern parts of India was compared for biomass and centellosides productivity under uniform agro-climatic conditions of the Indo-Gangetic plains at Lucknow. The highest biomass accumulation (411.9 g FW/m2 area) was recorded in accession A from north India, followed by 284.0, 135.7 and 29.2 g FW/m2 in accessions M, B and E from southern, eastern and north-eastern regions, respectively. Accession M possessed the highest asiaticoside content (52.1 mg/gDW) that was 1.58, 2.34 and 21.7 folds more than accessions A, B and E, respectively. The madecassoside level in leaves of accessions B and M was comparable (28.9 and 25.7 mg/gDW) and two folds more than accession A (13.9 mg/gDW). The madecassic and asiatic acid content in leaf tissue of all four accessions remained low in Lucknow. Amplified fragment length polymorphism (AFLP) analysis with 23 primers yielded 696 fragments, 563 of which were polymorphic. Accession M out-grouped with genetic dissimilarity indices of 83, 85 and 95% from accessions A, E and B, respectively. Commercial cultivation of accessions M and A through a four months growth cycle (June to September) in agro-climatic conditions of the Indo-Gangetic plains is suggested.

Protective mechanism of lignans from Phyllanthus amarus against galactosamine/ lipopolysaccharide-induced hepatitis: an in-vivo and in-silico studies.

Phyllanthus amarus is a medicinal herb used in traditional Indian medicine for liver disorders. Several researches also show that it acts primarily in the liver, but the molecules were unidentified for liver protective activity. This study was to determine whether the lignans isolated from P. amarus attenuates the D-galactosamine (GalN) / Lipopolysaccharide (LPS)- induced acute hepatitis in mice. Standardize mixture of lignans (slPA) isolated from leaves of P. amarus using automated chromatographic technique was used for experiments. Experimental mice were orally pre-treated with slPA (10, 30 and 100 mg/kg) for 7 days before intra-peritoneal injection of GalN/LPS. Acute hepatitis in mice was confirmed by significant increase of pro-inflammatory cytokines, and hepatotoxic markers. Pre-treatment of slPA exhibit significant liver protection in dose dependant mannaer. In-silico molecular docking studies also suggests that lignans are preferentially more active due to strong binding affinity against pro-inflammatory cytokines; IL-1ß, IL-6, and TNF-α. The electronic parameters of lignans for bioavailability, drug likeness and toxicity were within the acceptable limit. In-vivo and in-silico results suggest that pretreatment of slPA exhibit potent hepatoprotection against GalN/LPS-induced hepatitis in mice and the liver protective effects may be due to the inhibition of inflammatory mediators.

Antiplasmodial potential of extracts from two species of genus Blumea.

CONTEXT: A number of Blumea (Asteraceae) species are being used in traditional Chinese and Indian folklore medicines to cure various diseases including cancer, fungal and bacterial infections. OBJECTIVE: To evaluate the in vitro antiplasmodial potential and cytotoxicity of various extracts and fractions of B. membranacea DC and B. eriantha DC and high performance liquid chromatography (HPLC) chemical fingerprinting of their crude extracts. MATERIALS AND METHODS: The aerial parts and roots of B. membranacea and B. eriantha were extracted with ethanol and the extracts were successively partitioned with n-hexane, ethyl acetate and n-butanol, which were later evaluated for their in vitro antiplasmodial activity against Plasmodium falciparum NF-54 and in vitro cytotoxicities against non-cancerous Vero cell line. HPLC chemical fingerprinting was performed on extracts of B. membranacea and B. eriantha. RESULTS: The n-hexane (MA1), ethyl acetate (MA2) fractions of aerial parts and n-butanol (MR3) fraction of roots of B. membranacea showed IC50 values of 17.4, 19.0 and 3.3 µg/mL respectively, while the n-hexane (EA1), ethyl acetate (EA2) fractions of aerial parts and ethyl acetate (ER2) fraction of roots of B. eriantha showed IC50 values of 25.0, 26.5 and 15.6 µg/mL, respectively, against P. falciparum NF-54. All these fractions were non-toxic to Vero cells. DISCUSSION AND CONCLUSION: Both B. membranacea and B. eriantha possesses a high degree of selective antiplasmodial activity (selectivity index up to >60) and hence, may find their use in antimalarial phytopharmaceuticals as well as in discovery of a safer and novel antimalarial lead.

Quantitative determination of bioactive 4-hydroxy-α-tetralone, tetralone-4-O-ß-D-glucopyranoside and ellagic acid in Ammannia baccifera (Linn.) by reversed-phase high-performance liquid chromatography.

Ammannia baccifera is an important component of various Chinese herbal formulations for which a rapid, simple, sensitive, gradient and reproducible reversed-phase high-performance liquid chromatographic method has been developed for the quantitative estimation of its bioactive constituents, 4-hydroxy-α-tetralone (4H), tetralone-4-O-ß-D-glucopyranoside (T4) and ellagic acid (EA). The chromatographic separation of samples was performed on a Chromatopak Peerless C18 (250 × 4.6 mm i.d., 5 µm) column by gradient elution with 0.1% trifluoroacetic acid in water and methanol at a flow rate of 0.6 mL/min, a column temperature at 25°C and ultraviolet detection at λ 254 nm. The limit of detection (LOD) and limit of quantification (LOQ) were 1.51 and 5.06 µg/mL for EA, 0.70 and 2.33 µg/mL for T4 and 0.22 and 0.73 µg/mL for 4H, respectively. Good results were achieved with respect to linearity (r(2) > 0.999), repeatability (relative standard deviation ≤ 1.73%) and recovery (99.06-100.76%). The method was validated for linearity, accuracy, repeatability, LOQ and LOD. The method is simple, accurate and precise and was successfully applied to the analysis of these three analytes in five different leaf and root samples of A. baccifera; the method may be recommended for routine quality control analysis of various Chinese herbal formulations containing A. baccifera.

Influence of cellular differentiation and elicitation on intermediate and late steps of terpenoid indole alkaloid biosynthesis in Catharanthus roseus.

The invaluable antineoplastic bisindole alkaloids of Catharanthus roseus and their precursor, vindoline, are not produced in cell cultures. The intricacies involved in endogenous (cellular differentiation) and exogenous (elicitation) regulation of their biosynthesis need to be dissected out for favorable exploitation. This study aimed at elucidating the effect of Pythium aphanidermatum homogenate and methyl jasmonate (MeJa) on in vitro cultures (of cv. 'Dhawal') representing increasing level of differentiation (suspension < callus < shoots) in terms of alkaloid accumulation and transcript abundance of strictosidine beta-D: -glucosidase (SGD) and acetyl-CoA: 4-O-deacetylvindoline 4-O-acetyl-transferase (DAT) genes, representing intermediate and late steps, respectively, of terpenoid indole alkaloid biosynthesis. Elicitation of suspension cultures caused transcriptional upregulation of SGD and enhanced the accumulation of total alkaloids but did not produce vindoline as DAT transcripts were always found to be absent in suspension-cultured cells. Vindoline was also not detected in unelicited and MeJa-treated callus but appeared upon elicitation with fungal homogenate for 24 h that coincided with maximal DAT transcription. Transcript levels of both genes increased upon elicitation of callus but remained below levels present in the mature plant leaf. Elicitation caused appearance of vindoline in shoots and increased the transcript abundance of both genes beyond levels observed in the mature plant leaf. Differentiation was essential for expression of DAT but not SGD, and vindoline biosynthetic potential increased with it.

Simultaneous quantification of withanolides in Withania somnifera by a validated high-performance thin-layer chromatographic method.

This paper describes a sensitive, selective, specific, robust, and validated densitometric high-performance thin-layer chromatographic (HPTLC) method for the simultaneous determination of 3 key withanolides, namely, withaferin-A, 12-deoxywithastramonolide, and withanolide-A, in Ashwagandha (Withania somnifera) plant samples. The separation was performed on aluminum-backed silica gel 60F254 HPTLC plates using dichloromethane-methanol-acetone-diethyl ether (15 + 1 + 1 + 1, v/v/v/v) as the mobile phase. The withanolides were quantified by densitometry in the reflection/absorption mode at 230 nm. Precise and accurate quantification could be performed in the linear working concentration range of 66-330 ng/band with good correlation (r2 = 0.997, 0.999, and 0.996, respectively). The method was validated for recovery, precision, accuracy, robustness, limit of detection, limit of quantitation, and specificity according to International Conference on Harmonization guidelines. Specificity of quantification was confirmed using retention factor (Rf) values, UV-Vis spectral correlation, and electrospray ionization mass spectra of marker compounds in sample tracks.

Iridoid glycosides from Gmelina arborea.

Three iridoid glycosides 6-O-(3''-O-benzoyl)-alpha-L-rhamnopyranosylcatalpol (1a), 6-O-(3''-O-trans-cinnamoyl)-alpha-L-rhamnopyranosylcatalpol (2a) and 6-O-(3''-O-cis-cinnamoyl)-alpha-L-rhamnopyranosylcatalpol (3a) were isolated from aerial parts of Gmelina arborea and structures were elucidated by spectral analysis. Additionally a known iridoid 6-O-(3'', 4''-O-dibenzoyl)-alpha-L-rhamnopyranosylcatalpol (4) was also isolated and identified.

Iridoid glycoside-based quantitative chromatographic fingerprint analysis: a rational approach for quality assessment of Indian medicinal plant Gambhari (Gmelina arborea).

A sensitive, selective and robust qualitative and quantitative densitometric high-performance thin layer chromatographic method was developed and validated for the determination of iridoid glycoside in the aerial part of Gambhari (Gmelina arborea). Iridoid gycoside 6-O-(2'',3''-dibenzoyl)-alpha-l-rhamnopyranosylcatalpol (IG) was used as a chemical marker for the standardization of G. arborea plant extracts. The separation was performed on aluminum Kieselgel 60F254 TLC plates using chloroform-methanol as mobile phase. The quantitation of IG was carried out using the densitometric reflection/absorption mode at 240 and 430 nm after post-chromatographic derivatization with vanillin-sulphuric acid reagent. A precise and accurate quantification can be performed in the linear working concentration range of 1000-5000 ng/spot with good correlation (r2=0.994). The method was validated for peak purities, precision, robustness, limit of detection (LOD) and quantitation (LOQ), etc., as per ICH guidelines. Specificity of quantitation was confirmed using retention factor (R(f)), UV-vis spectral correlation and ESI-MS spectra of marker compound (IG) in sample track.

Separation and quantification of lignans in Phyllanthus species by a simple chiral densitometric method.

A sensitive, selective, and robust high-performance TLC (HPTLC) method using chiral TLC plates for qualitative and quantitative analysis of phyllanthin (A), hypophyllanthin (B), niranthin (C), and nirtetralin (D), the active lignans of Phyllanthus species, was developed and validated. The effectiveness and role of various stationary phases viz TLC silica gel 60F(254), HPTLC silica gel 60F(254), and chiral TLC plates in the quantitation were evaluated. A precoated chiral TLC plate was found suitable for the simultaneous analysis of four pharmacologically active lignans. For achieving good separation, the optimized mobile phase of n-hexane/acetone/1,4-dioxane (9:1:0.5 by volume) was used (R(f) = 0.30, 0.36, 0.41, and 0.48 for compounds A, B, C, and D, respectively). A densitometric determination of the above compounds was carried out in reflection/absorption mode at 620 nm. Optimized chromatographic conditions provide well-separated compact bands for the tested lignans. The calibration curves were found linear in the concentration range of 100-500 ng/band. Recoveries of A-D were 99.98, 100.51, 99.22, and 98.74%, respectively. The method was validated according to ICH guidelines. The method reported here is reproducible and applied for the quantitative analysis of the above lignans in the leaves of four Phyllanthus species, i. e., P. amarus, P. maderaspatensis, P. urinaria, and P. virgatus.

High-performance thin-layer chromatographic method for quantitative determination of 4alpha-methyl-24beta-ethyl-5alpha-cholesta-14,25-dien-3beta-ol, 24beta-ethylcholesta-5,9(11),22E-trien-3beta-ol, and betulinic acid in Clerodendrum inerme.

A sensitive, selective, precise, and robust high-performance thin-layer chromatography method was developed and validated for analysis of two new recently isolated sterols, 4alpha-methyl-24beta-ethyl-5alpha-cholesta-14,25-dien-3beta-ol (1) and 24beta-ethylcholesta-5,9(11),22E-trien-3beta-ol (2), and a triterpene, betulinic acid (3), in Clerodendrum inerme extract. The method employed HPTLC plates precoated with silica gel 60F(254 )as the stationary phase. To achieve good separation, an optimised mobile phase consisting of toluene-acetone (94:06, v/v) was used (R(f )0.48, 0.34, and 0.22 for compounds 1, 2, and 3, respectively). Densitometric determination of the above compounds was carried out in reflection/absorption mode at 620 nm. Optimised chromatographic conditions provide well separated compact spots for the compounds 1, 2, and 3. The calibration curves were linear in the concentration range of 100-2500 ng/spot. The method was validated for precision, robustness, and recovery. The limits of detection and quantitation were 5, 6, and 10 microg/mL and 14, 18, and 29 microg/mL, respectively, for 1, 2, and 3. The method reported here is reproducible and convenient for quantitative analysis of these compounds in the aerial parts of C. inerme.

Quantitative determination of phyllanthin and hypophyllanthin in Phyllanthus species by high-performance thin layer chromatography.

A simple, precise and rapid high-performance thin-layer chromatographic method has been developed for the estimation of phyllanthin (1) and hypophyllanthin (2), the important lignans of Phyllanthus species, especially Phyllanthus amarus. Separation of 1 and 2 was carried out on silica gel 60 F254 layers eluted with hexane:acetone:ethyl acetate (74:12:8), and the analytes were visualised through colour development with vanillin in concentrated sulphuric acid and ethanol. Scanning and quantification of spots was performed at 580 nm. Recoveries of 1 and 2 were 98.7 and 97.3%, respectively. The method was validated and the peak purities and limits of detection and quantification were determined.

Liquid chromatographic determination of sennosides in Cassia angustifolia leaves.

A simple liquid chromatographic method was developed for the determination of sennosides B and A in leaves of Cassia angustifolia. These compounds were extracted from leaves with a mixture of methanol-water (70 + 30, v/v) after defatting with hexane. Analyte separation and quantitation were achieved by gradient reversed-phase liquid chromatography and UV absorbance at 270 nm using a photodiode array detector. The method involves the use of an RP-18 Lichrocart reversed-phase column (5 microm, 125 x 4.0 mm id) and a binary gradient mobile-phase profile. The various other aspects of analysis, namely, peak purity, similarity, recovery, repeatability, and robustness, were validated. Average recoveries of 98.5 and 98.6%, with a coefficient of variation of 0.8 and 0.3%, were obtained by spiking sample solution with 3 different concentration solutions of standards (60, 100, and 200 microg/mL). Detection limits were 10 microg/mL for sennoside B and 35 microg/mL for sennoside A, present in the sample solution. The quantitation limits were 28 and 100 microg/mL. The analytical method was applied to a large number of senna leaf samples. The new method provides a reliable tool for rapid screening of C. angustifolia samples in large numbers, which is needed in breeding/genetic engineering and genetic mapping experiments.

Neo-clerodane diterpenoids from Clerodendrum inerme.

Three neo-clerodane diterpenoids, inermes A, B and 14,15-dihydro-15 beta-methoxy-3-epicaryoptin, have been isolated from the hexane extract of the leaves of Clerodendrum inerme in addition to an epimeric mixture of 14,15-dihydro-15-hydroxy-3-epicaryoptin. Structures of these compounds have been elucidated on the basis of spectral studies.

Chemical fingerprinting of Andrographis paniculata using HPLC, HPTLC and densitometry.

An attempt has been made to develop a method by which to determine the chemical fingerprint of Andrographis paniculata (Acanthaceae). High-performance thin layer chromatography (HPTLC) was used to analyse hexane, chloroform, methanol and water extracts of leaves of A. paniculata. A computerised densitometer was applied to the two-dimensional spectrographic image analysis of the HPTLC plates. An HPLC equipped with a photodiode array detector was used for the analyses of these different extracts. The analyses showed that andrographolide and neoandrographolide are absent in the hexane extract but are present in greater amounts in the methanol extract as compared with the other extracts. These chromatograms may serve as a chemical fingerprint of the drug A. paniculata for quality control purposes and in the preparation of formulations based on the drug.

4alpha-methyl-24beta-ethyl-5alpha-cholesta-14,25-dien-3beta-ol and 24beta-ethylcholesta-5, 9(11), 22E-trien-3beta-ol, sterols from Clerodendrum inerme.

From the aerial parts of Clerodendrum inerme, two new sterols (4alpha-methyl-24beta-ethyl-5alpha-cholesta-14, 25-dien-3beta-ol and 24beta-ethylcholesta-5, 9(11), 22E-trien-3beta-ol) and a new aliphatic ketone (11-pentacosanone) were isolated together with another known aliphatic ketone (6-nonacosanone) and a diterpene (clerodermic acid). The structure elucidations were based on analyses of physical and spectroscopic data.