Urinary MicroRNA biomarkers of nephrotoxicity in Macaca fascicularis.

Drug-induced kidney injury (DIKI) refers to kidney damage resulting from the administration of medications. The aim of this project was to identify reliable urinary microRNA (miRNAs) biomarkers that can be used as potential predictors of DIKI before disease diagnosis. This study quantified a panel of six miRNAs (miRs-210-3p, 423-5p, 143-3p, 130b-3p, 486-5p, 193a-3p) across multiple time points using urinary samples from a previous investigation evaluating effects of a nephrotoxicant in cynomolgus monkeys. Exosome-associated miRNA exhibited distinctive trends when compared to miRNAs quantified in whole urine, which may reflect a different urinary excretion mechanism of miRNAs than those released passively into the urine. Although further research and mechanistic studies are required to elucidate how these miRNAs regulate signaling in disease pathways, we present, for the first time, data that several miRNAs displayed strong correlations with histopathology scores, thus indicating their potential use as biomarkers to predict the development of DIKI in preclinical studies and clinical trials. Also, these findings can potentially be translated into other non-clinical species or human for the detection of DIKI.

Angiographic Patterns of Young Patients with Coronary Artery Disease in an Indian Population.

BACKGROUND: The incidence of coronary artery disease has continued to rise in recent decades, even in the developing world, affecting a broad spectrum of the population including young adults less than forty years. This is attributable to the rise in prevalence of conventional risk factors like diabetes mellitus, hypertension, smoking, dyslipidemia, and obesity. Although a significant number of studies have been done on the angiographic profile of patients with coronary artery disease, only a few of these studies were done in young patients and most of the studies were limited to northern India. AIMS AND OBJECTIVES: In this study, we aimed to determine the angiographic profile of young patients ≤ 40 years in a tertiary care centre in southern India. MATERIALS AND METHODS: A retrospective analytic study was conducted at the Meditrina Specialist Hospital, Kollam, Kerala, India. Individuals of both genders with age ≤ 40 years who were diagnosed with coronary artery disease between June 2021 and May 2022 were included. RESULTS: A total of 74 patients were included, out of which 62 were male and 12 were female. The mean ± SD age of the participants studied was 36.38 ± 3.99 years Amongst patients who had significant coronary artery disease, 24 (57.14%) had single vessel disease, 13 (31.00%) had double vessel disease, and 5 (11.86%) had triple vessel disease. The left anterior descending (LAD) artery was found to be the most frequently involved in all patterns of coronary artery disease (CAD). Male gender and diabetes were the most common risk factors for CAD present in 29.3% of patients studied. CONCLUSION: Male gender and diabetes were responsible for the relatively high incidence of premature CAD in this study with single vessel disease being the most prevalent finding. The LAD artery was the most commonly affected followed by RCA and LCX with right PLB being the least vessel involved.

CONTEXTE: L'incidence de la maladie coronarienne n'a cessé d'augmenter, touchant un large éventail de la population, y compris les jeunes adultes de moins de quarante ans au cours des dernières décennies, même dans le monde en développement. Cela est attribuable à l'augmentation de la prévalence de facteurs de risque conventionnels tels que le diabète sucré, l'hypertension, le tabagisme, la dyslipidémie et l'obésité. Bien qu'un nombre significatif d'études aient été réalisées sur le profil angiographique des patients atteints de maladie coronarienne, seules quelques-unes de ces études ont porté sur des patients jeunes et la plupart des études étaient limitées au nord de l'Inde. OBJECTIFS: Dans cette étude, nous visons à déterminer le profil angiographique des jeunes patients de ≤ 40 ans dans un centre de soins tertiaires du sud de l'Inde. MATÉRIAUX ET MÉTHODES: Une étude analytique rétrospective a été menée à l'hôpital spécialisé Medtrina de Kollam, Kerala, Inde. Les individus de deux sexes âgés de ≤ 40 ans, diagnostiqués avec une maladie coronarienne entre juin 2021 et mai 2022, ont été inclus. RÉSULTATS: Au total, 74 patients ont été inclus, parmi lesquels 62 étaient des hommes et 12 étaient des femmes. L'âge moyen ± SD des participants était de 36,38 ± 3,99 ans. Parmi les patients présentant une maladie coronarienne significative, 24 patients (57,14 %) avaient une maladie à un seul vaisseau, 13 patients (31,00 %) avaient une maladie à deux vaisseaux et 5 patients (11,86 %) avaient une maladie à trois vaisseaux. L'artère interventriculaire antérieure (LAD) était la plus fréquemment impliquée dans tous les types de maladie coronarienne (MC). Le sexe masculin et le diabète étaient les facteurs de risque les plus courants pour la MC, présents chez 29,3 % des patients étudiés. CONCLUSION: Le sexe masculin et le diabète étaient responsables de l'incidence relativement élevée de la MC précoce dans cette étude, la maladie à un seul vaisseau étant la constatation la plus courante. L'implication de la LAD est la plus fréquente, suivie de la RCA et de la LCX, la branche droite PLB étant la moins impliquée. MOTS-CLÉS: Maladie coronarienne; Angiographie coronaire, Profil ; Jeunes, Population indienne.

Donor-transmitted cystinuria in a renal transplant recipient.

Cystinuria is an autosomal recessive disorder associated with defective proximal tubular reabsorption of divalent amino acids. It leads to increased cystine, ornithine, lysine, and arginine excretion in the urine. Cystine is insoluble in physiological pH, and cystinuria leads to crystalluria and nephrolithiasis. We present a case of acquired cystinuria in a renal transplant recipient, that is, to the best of our knowledge, the first case of acquired cystinuria ever documented in the literature.

Bifunctional g-C3N4/carbon nanotubes/WO3 ternary nanohybrids for photocatalytic energy and environmental applications.

Ternary nanohybrids based on mesoporous graphitic carbon nitride (g-C3N4) were synthesized and presented for developing stable and efficient Hydrogen (H2) production system. Based on photocatalytic activity, optimization was performed in three different stages to develop carbon nanotubes (CNTs) and WO3 loaded g-C3N4 (CWG-3). Initially, the effect of exfoliation was investigated, and a maximum specific surface area of 100.77 m2/g was achieved. 2D-2D interface between WO3 and g-C3N4 was targeted and achieved, to construct a highly efficient direct Z-scheme heterojunction. Optimized binary composite holds the enhanced activity of about 2.6 folds of H2 generation rates than the thermally exfoliated g-C3N4. Further, CNT loading towards binary composite in an optimized weight ratio enhances the activity by 6.86 folds than the pristine g-C3N4. Notably, optimized ternary nanohybrid generates 15,918 µmol h-1. g-1cat of molecular H2, under natural solar light irradiation with 5 vol% TEOA as a sacrificial agent. Constructive enhancements deliver remarkable H2 production and dye degradation activities. Results evident that, the same system can be useful for pilot-scale energy generation and other photocatalytic applications as well.

DNA binding, antioxidant activity, and DNA damage protection of chiral macrocyclic Mn(III) salen complexes.

We are reporting the synthesis, characterization, and calf thymus DNA binding studies of novel chiral macrocyclic Mn(III) salen complexes S-1, R-1, S-2, and R-2. These chiral complexes showed ability to bind with DNA, where complex S-1 exhibits the highest DNA binding constant 1.20 × 10(6) M(-1). All the compounds were screened for superoxide and hydroxyl radical scavenging activities; among them, complex S-1 exhibited significant activity with IC(50) 1.36 and 2.37 µM, respectively. Further, comet assay was used to evaluate the DNA damage protection in white blood cells against the reactive oxygen species wherein complex S-1 was found effective in protecting the hydroxyl radicals mediated plasmid and white blood cells DNA damage.

Chiral discrimination asserted by enantiomers of Ni (II), Cu (II) and Zn (II) Schiff base complexes in DNA binding, antioxidant and antibacterial activities.

Chiral Schiff base ligands (S)-H(2)L and (R)-H(2)L and their complexes (S-Ni-L, R-Ni-L, S-Cu-L, R-Cu-L, S-Zn-L and R-Zn-L) were synthesized, characterized and examined for their DNA binding, antioxidant and antibacterial activities. The complexes showed higher binding affinity to calf thymus DNA with binding constant ranging from 2.0×10(5) to 4.5×10(6) M(-1). All the complexes also exhibited remarkable superoxide (56-99%) and hydroxyl scavenging (45-89%) activities as well as antibacterial activities against gram (+) and gram (-) bacteria. However, none of the complexes showed antifungal activity. Conclusively, S enantiomers of the complexes were found to be relatively more efficient for DNA interaction, antioxidant and antibacterial activities than their R enantiomers. This study reveals the possible utilization of chiral Schiff base complexes for pharmaceutical applications.

Enantioselective cyanosilylation of ketones catalyzed by recyclable polymeric and dimeric Mn(III) salen complexes at room temperature.

Recyclable polymeric 1 and dimeric 2 chiral Mn(III) salen complexes catalyzed enantioselective cyanosilylation of various ketones in the presence of triphenylphosphine oxide as an additive proceeded smoothly at room temperature, providing excellent yields (up to 98%) and enantiomeric excess (up to 86%) of respective cyanohydrin trimethylsilyl ether. For most of the substrates, the Catalyst 1 showed slightly better reactivity and enantioselecitivity than the Catalyst 2 nevertheless both the catalysts were easily recovered and reused four times with the retention of their efficiency.

Chiral recyclable dimeric and polymeric Cr(III) salen complexes catalyzed aminolytic kinetic resolution of trans-aromatic epoxides under microwave irradiation.

Aminolytic kinetic resolution (AKR) of trans-stilbene oxide and trans-beta-methyl styrene oxide proceeded smoothly under microwave irradiation using chiral dimeric and polymeric Cr(III) salen complexes as efficient catalysts, giving regio-, diastereo-, and enantioselective anti-beta-amino alcohols in high yields (49%) and chiral purity (ee up to 94%) in case of 4-methylaniline within 2 min. The kinetic resolution system is approximately five times faster than traditional oil bath heating at 70 degrees C and 420 times faster than the reaction conducted at room temperature with concomitant recovery of respective chirally enriched epoxides (ee, 92%) in excellent yields (up to 48%). The catalyst 1 worked well in terms of enantioselectivity than the catalyst 2, but both the catalysts were easily recovered and reused five times with the retention of its efficiency.

Uptake of molybdate by adsorption onto industrial solid waste Fe(III)/Cr(III) hydroxide: kinetic and equilibrium studies.

Removal of molybdate on to industrial solid waste Fe(III)/Cr(III) hydroxide as adsorbent has been investigated. Pretreated adsorbent was found to be more efficient in the uptake of molybdate compared to untreated adsorbent. Effect of pH on the adsorption was studied in the pH range 4.0 to 10.0. Optimum pH for maximum removal was found to be 4.0. Langmuir and Freundlich isotherm models were used to study the adsorption capacity of the adsorbent. The adsorption follows second order kinetics. No significant effect of temperature has been observed. Desorption studies showed that ion exchange mechanism is predominant.

Recycling Fe(III)/Cr(III) hydroxide, an industrial solid waste for the removal of phosphate from water.

Industrial solid waste, Fe(III)/Cr(III) hydroxide, was investigated to assess the capacity for the removal of phosphate from aqueous solution. Langmuir and Freundlich isotherms were used to model the adsorption equilibrium data. The system follows both isotherms. Adsorption capacity was found to be 6.5 mg/g. Kinetic studies show that the adsorption obeyed second order kinetics. Thermodynamic parameters were evaluated. Overall adsorption process was endothermic and spontaneous. Optimum pH for phosphate adsorption was found to be 4.0. Effect of coexisting anions has also been examined.

Regulation of urokinase receptor expression by phosphoglycerate kinase.

Post-transcriptional regulation represents a major mechanism by which eukaryotic gene expression is regulated through cis-trans interactions that serve as signals for rapid alterations of messenger RNA (mRNA) stability. Regulation of urokinase-type plasminogen activator receptor (uPAR) mRNA involves the interaction of a uPAR mRNA coding region sequence with a 50 kD uPAR mRNA binding protein. We purified this protein from human bronchial epithelial (Beas2B) cells and identified it as phosphoglycerate kinase (PGK). We cloned PGK cDNA by polymerase chain reaction and expressed the recombinant PGK protein, which specifically bound the uPAR mRNA coding region by gel mobility shift and Northwestern blotting. We also confirmed a direct interaction of PGK protein with uPAR mRNA by immunoprecipitation. Overexpression of PGK in uPAR-overproducing H157 lung carcinoma cells resulted in decreased cytoplasmic uPAR mRNA and cell surface uPAR protein expression. Reduced uPAR mRNA expression involved decreased stability of the uPAR mRNA. Decline in 3H-thymidine incorporation and migration occurred in H157 cells transfected with PGK cDNA. These results demonstrate that PGK regulates uPAR expression at the post-transcriptional level.

Localized amyloidosis in nasopharyngeal carcinoma.

A study of biopsies from 434 consecutive primary nasopharyngeal carcinomas revealed amyloid deposits in 54 (12%) of the tumours. Amyloid was present in all three histological types of nasopharyngeal carcinoma, but was more frequently observed in nonkeratinizing carcinomas. The amyloid deposits were patchy in distribution and occurred both within tumour cells and extracellularly. A neoplastic origin for this form of amyloid is suggested.

Hepatitis B virus surface antigen in glomerular immune complex deposits of patients with systemic lupus erythematosus.

In view of a high prevalence of hepatitis B virus infection in the Malaysian population, indirect immunofluorescence examination for hepatitis B surface antigen (HBsAg) was routinely performed on renal biopsy specimen at the University Hospital, Kuala Lumpur, over a 3-year period. Examination of renal tissue from 259 patients, including 47 with systemic lupus erythematosus (SLE), revealed 43 cases with HBsAg in glomerular immune complexes. A significantly high proportion (30/43) of these were SLE patients. The deposits were granular in nature, situated in both the capillary walls and mesangium and associated with immunoglobulin deposition. Morphological patterns of lupus nephritis involved were focal proliferative (one case), diffuse proliferative (23 cases) and membranous (six cases). None of these patients showed clinical evidence of liver disease. The significance of these findings remains uncertain, but the possibility exists that the hepatitis B virus may have a role in the pathogenesis of SLE in the tropics where both SLE and HBs antigenaemia are common.

Morphological patterns of glomerular disease in renal biopsies from 1000 Malaysian patients.

Adequately biopsied renal tissue received in the Department of Pathology, University Hospital, Kuala Lumpur from 1,000 consecutive Malaysian patients during an eleven year period between 1970 and 1981 was reviewed. The youngest patient was 6 days old and the oldest 80 years. Both sexes were equally represented. The majority of the patients were Chinese (71%) with Malays and Indians comprising most of the remainder. Over half the patients (50.4%) presented with the nephrotic syndrome. Other modes of presentation included systemic lupus erythematosus, proteinuria and haematuria separately or in combination and hypertension. Minimal change (25.7%) and proliferative glomerulonephritis (24.8%) were present in about equal numbers and together accounted for over half of the cases (50.5%). Lupus nephritis was the third most common diagnosis (18.4%). In addition, there were patients with focal glomerulonephritis (5.4%), membranous glomerulonephritis (5.5%), Berger's disease (5.8%), amyloidosis (0.6%) and end stage renal disease (4.0%).

Lupus nephritis and lupus band test.

Twenty-seven patients with histologically confirmed lupus nephritis were studied to identify the incidence of lupus band and its significance to histological patterns of nephritis and complement levels. It was found that the kidney involvement is 2.5 times more frequent in lupus band positive patients. The association of a positive lupus and low C3 level signifies the presence of diffuse proliferative glomerulonephritis rather than membranous glomerulonephritis. The results, together with earlier reports, are discussed.

The efficacy of potassium-induced cardioplegia and topical hypothermia in the correction of congenital cardiac lesions.

Myocardial metabolic, structural and functional preservation were evaluated in 44 patients who underwent open heart surgery under cardiopulmonary bypass, potassium cardioplegia and topical hypothermia. The duration of cardiac arrest varied from 14 to 87 minutes. Myocardial high-energy phosphates were not only adequately preserved but actually exceeded the control values during periods of cardiac arrest. Glycogen levels were decreased moderately and one to three fold increases in lactate/pyruvate ratios were detected. Myocardial ultrastructure was well preserved. Postoperative clinical recovery of the patients was excellent. The only patient who died from a low output syndrome showed no evidence of myocardial damage. The results of this study serve to illustrate the beneficial effects of potassium cardioplegia and topical hypothermia on myocardial preservation during prolonged periods of ischaemic cardiac arrest, as used for the correction of congenital cardiac lesions.

Pentastomiasis.

Pentastomiasis is a zoonotic parasitic disease of man, first described by Pruner in 1847. The causative organisms are pentastomes (pentastomids), so called because of the presence of two pairs of anterior hooks and a mouth, which give the appearance of 5 openings. They are annulated but non segmented vermiform blood-sucking endoparasites. They are probably best classified as a separate phyllum, the Pentastomida. Of medical interest are two families of pentastomes namely Linguatulidae and Porocephalidae, of which species of the genera Linguatula and Armillifer (Porocephalus) are parasites of man.

Advanced retinoblastoma in Malaysian children.

Twenty children with retinoblastoma are reviewed who were treated at the University Hospital, Kuala Lumpur over a 10-year-period. They constitute 6.6% of childhood malignancies and without exception all presented with advanced disease. Hereditary cases were notably absent in the the series probably because past cases have almost invariably succumbed without an opportunity to transmit the gene. With enucleation and radiotherapy six of the patients have survived from 2 to 12 years. The addition of vincristine and cyclophosphamide has not been associated with improved survival.