Chemical Profile, Antibacterial Activity and Antioxidant Activity of Bark Volatile Oil of Terminalia arjuna.

Terminalia arjuna is an evergreen medicinal plant that belongs to the Combretaceae family of flowering plants. The bark of the plant exhibits antiviral, anticancer, hypocholesterolemic, antioxidant and antimicrobial properties. In this study, composition antibacterial activity, antioxidant activity and cytotoxicity of bark oil of Terminalia Arjuna (Roxb.) were reported. Oils were extracted by microwave assisted hydrodistillation where an oil yield of 0.18% was obtained followed by the identification of 35 compounds by gas chromatography mass spectrometry. The most abundant volatiles were furfural (11.11%), isoeugenol (9.99%), p-ethylguaiacol (9.97%), α-cadinol (9.57%), and estragole (9.47%). The oil was further evaluated against ten different drug resistant strains where oil showed significant activity against all pathogens and the highest activity was found against Acinetobacter baumannii (22mm), Klebsiella pneumoniae (22mm) and Staphylococcus aureus (22mm) in a concentration-dependent manner. Antioxidant activity evaluation demonstrated 68% radical scavenging activity by the volatile oil as compared to 81% of the standard, ascorbic acid at a concentration of 1000 µg. Cytotoxicity studies were conducted to see the effect of sample on the expression level of a housekeeping gene, Glyceraldehyde 3-phosphate dehydrogenase where it did not affect the normal transcription of the gene.

Clinicopathological characteristics and renal outcomes of adult patients with pauci-immune necrotizing glomerulonephritis according to ANCA status.

BACKGROUND: Pauci-immune necrotizing glomerulonephritis (PING) is commonly associated with the presence of antineutrophilic cytoplasmic antibodies (ANCAs) but a significant number of patients do not have these antibodies. The significance of ANCA-negativity in the context of Berden's classification of PING is not known. METHODS: A retrospective analysis was conducted on all patients with histopathological diagnosis of idiopathic PING irrespective of ANCA status diagnosed between January 1998 to December 2018 and followed up at renal clinic for > 12 months. All biopsies were reclassified by Berden's classification. Clinicopathological characteristics and renal outcomes of ANCA-positive and ANCA-negative patients were compared. RESULTS: Out of 134 patients, 66 (49.5%) were ANCA-negative. The mean age was 34.76 ± 13.3 years. Compared with the ANCA-positive patients, ANCA-negative patients had significantly greater prevalence of nephrotic-range proteinuria (74.23% Vs 57.9%, P = 0.036) with less extra-renal manifestations (P < 0.05)). On histology, focal and crescentic classes dominated with less number of globally sclerosed glomeruli (2.7% Vs 5.07%, P = 0.02) and more mesangial proliferation (22.7% Vs 4.41%, P = 0.002) in the ANCA-negative group, whereas sclerotic was predominant in the ANCA-positive group (P = 0.05). More patients achieved complete and partial recovery in ANCA-negative patients (42.4% Vs 20.5%, P < 0.05) with better renal survival (27.27% Vs 16.17%, log-rank test: P = 0.03) and less patient mortality (13.63% vs 30.8%, log-rank test: P = 0.04) at 2 years. CONCLUSION: Our study confirms high prevalence of ANCA negativity among our cohort and this group presents with isolated renal involvement with better renal and patient survival. The ANCA-positive group showed significantly more patients in the sclerotic class, lower 2-year renal survival, and higher 2-year mortality as compared to the ANCA-negative group. However, the complete and partial responses to treatment were significantly better in the ANCA-negative group. Key Points • This study shows a high prevalence of ANCA negativity in cases of PING in Pakistani population, as almost half of patients in this study did not have these antibodies. • This negativity is more prevalent in the Asian populations but its significance in the context of Berden's classification of PING is unknown. • ANCA-negative group exhibited less severe phenotype and better outcomes compared with ANCA-positive group.

Maternal and fetal outcomes in pregnancy complicated by pre-existing lupus nephritis: Insights from a developing country Pakistan.

BACKGROUND: Pregnancy in women with systemic lupus erythematosus (SLE) has remained a great challenge for clinicians in terms of maternal and fetal outcomes. The outcomes in women with pre-existing lupus nephritis (LN) are variable. The impact of different classes of LN on maternal and fetal outcomes during pregnancy is not well defined, as data is very scarce, especially from the developing countries. METHODS: A retrospective analysis was conducted on 52 women with 89 pregnancies. All had biopsy-proven LN. Those women who conceived at least 6 months after the diagnosis were included. The analysis was conducted between July 1998 and June 2018 at Sindh Institute of Urology and Transplantation (SIUT), evaluating the outcomes for both the mother and the fetus with a minimum follow-up of 12 months after child birth. RESULTS: The mean maternal age at SLE diagnosis was 21.45 ± 6 years and at first pregnancy was 26.49 ± 5.63 years. The mean disease duration was 14.02 ± 19.8 months. At conception, 47 (52.8%) women were hypertensive, 9 (10%) had active disease while 38 (42.7%) and 42 (47.2%) were in complete and partial remission, respectively. A total of 17 (19.1%) were on mycophenolate mofetil (MMF), which was switched to azathioprine (AZA). Out of 89 pregnancies, 56 (62.9%) were successful, while 33 (37.07%) had fetal complications like spontaneous abortion, stillbirth, perinatal death, and intrauterine growth retardation (IUGR). There were more vaginal deliveries (33 [58.92%]) than caesarean sections (23 [41.07%]). Renal flare was observed in 33 (37.1%) women while 15 (16.9%) developed pre-eclampsia. Proliferative LN was found in 56 (62.9%) cases, but no significant differences were found in maternal and fetal outcomes in relation to LN classes (p = .58). However, disease outcomes at 12 months were significantly poor in those with active disease at the time of conception (p < .05). There was only one maternal death. A total of 10 (11.2%) women showed deterioration in renal function and 5 (5.6%) were dialysis-dependent at 12 months. CONCLUSION: The maternal and fetal outcomes in pre-existing LN depend on the disease activity at the time of conception. No correlation was found between International Society of Nephrology/Renal Pathology Society (ISN/RPS) classes of LN and adverse disease and pregnancy outcomes.

Tetra-azolium salts induce significant cytotoxicity in human colon cancer cells, in vitro.

BACKGROUND: Azolium salts are the organic salts used as stable precursors for generating N-Heterocyclic Carbenes and their metal complexes. Azolium salts have also been reported to have significant biological potential. Hence, in the current study, four tetra-dentate azolium salts were derived from bis-azolium salts by a new synthetic strategy. METHODS: The tetra azolium salts have been synthesized by reacting the imidazole or methyl imidazole with dibromo xylene (meta, para)/ 1-bromo methyl imidazole or dibromo ethane resulting in the mono or bis azolium salts namely I-IV. V-VII have been obtained by reacting I with II-IV, resulting in the tetra azolium salts. Each product was analyzed by various analytical techniques, i.e., microanalysis, FT-IR, and NMR (1H & 13C). Salts V-VII were evaluated for their antiproliferative effect against human colon cancer cells (HCT-116) using MTT assay. RESULTS: Four chemical shifts for acidic protons between 8.5-9.5 δ ppm in 1H NMR and resonance of respective carbons around 136-146 δ ppm in 13C NMR indicated the successful synthesis of tetra azolium salts. Salt V showed the highest IC50 value, 24.8 µM among all synthesized compounds. CONCLUSION: Tetra-azolium salts may play a better cytotoxicity effect compared to mono-, bi-& tri-azolium salts.

Molecular modeling and simulation of transition metal-doped molybdenum disulfide biomarkers in exhaled gases for early detection of lung cancer.

BACKGROUND: The presence of volatile organic compounds (VOCs) in the exhaled breath of lung cancer patients is the only available source for detecting the disease at its initial stage. Exhaled breath analysis depends purely on the performance of the biosensors. The interaction between VOCs and pristine MoS2 is repulsive in nature. Therefore, modifying MoS2 via surficial adsorption of the transition metal nickel is of prime importance. The surficial interaction of six VOCs with Ni-doped MoS2 led to substantial variations in the structural and optoelectronic properties compared to those of the pristine monolayer. The remarkable improvement in the conductivity, thermostability, good sensing response, and recovery time of the sensor exposed to six VOCs revealed that a Ni-doped MoS2 exhibits impressive properties for the detection of exhaled gases. Different temperatures have a significant impact on the recovery time. Humidity has no effect on the detection of exhaled gases upon exposure to VOCs. The obtained results may encourage the use of exhaled breath sensors by experimentalists and oncologists to enable potential advancements in lung cancer detection. METHODS: The surface adsorption of transition metal and its interaction with volatile organic compounds on a MoS2 surface was studied by using Spanish Initiative for Electronic Simulations with Thousands of Atoms (SIESTA). The pseudopotentials used in the SIESTA calculations are norm-conserving in their fully nonlocal forms. The atomic orbitals with finite support were used as a basis set, allowing unlimited multiple-zeta and angular momenta, polarization, and off-site orbitals. These basis sets are the key for calculating the Hamiltonian and overlap matrices in O(N) operations. The present hybrid density functional theory (DFT) is a combination of PW92 and RPBE methods. Additionally, the DFT+U approach was employed to accurately ascertain the coulombic repulsion in the transition elements.

Rosai Dorfman Disease With Extensive Bony Involvement- A Diagnostic Dilemma.

Previously classified as Non Langerhan cell histiocytosis by the Working Group of Histiocytic Society in 1987 Rosai Dorfman Destombes disease was first described by Destombes in 1965 and later in 1969 by Rosai and Dorfman as a rare histiocytic disorder with sinus histiocytosis and massive lymphadenopathy. They exist in both nodal and extranodal forms. Immunohistochemistry is an essential part of diagnosis to differentiate between Langerhans cell histiocytosis and another malignant histiocytosis. Some overlap has also been reported with IgG4-related diseases. We hereby reflect upon a patient who presented to our facility with pyrexia of unknown origin, the challenges faced to reach a diagnosis and the management offered.

Clinical Course and Long-term Outcome of Adults with Primary Focal Segmental Glomerulosclerosis: A Retrospective Cohort Study.

INTRODUCTION: Focal segmental glomerulosclerosis (FSGS) is one of the common causes of end-stage kidney disease (ESKD) in adults with primary glomerular diseases. Information on clinical course and long-term renal outcome of primary FSGS in adults are scanty. We aimed to determine the clinical course and long-term outcome of primary FSGS in a large number of adult patients from a tertiary care kidney center in Pakistan. METHODS: A retrospective review of the clinical charts of all adults (≥ 16 years) with a biopsy proven diagnosis of FSGS presenting to Sindh Institute of Urology and Transplantation, Karachi, between January 1995 and December 2017 was carried out. Cases with secondary FSGS were excluded. Relevant data items were retrieved both at baseline and on last follow-up. RESULTS: Among 401 adults with primary FSGS, 144 (35.9%) were followed for a mean duration of 66.6 ± 27.4 months, out of which, 129 (89.5%) were treated with steroids and immunosuppressants. Response to steroids was obtained in 62 (48%) patients, while 67 (52%) showed no response. Among responders, 24/62 (38.7%) relapsed after a mean duration of 24.2 ± 23.2 weeks, who were re-treated with same dose of steroids alone or combined with cyclosporine and all achieved remission. The long-term outcomes were significantly different between steroid responsive and nonresponsive cohorts. None of the patients in steroid responsive group developed ESKD or died, while 7 (10.4%) patients in nonresponsive group developed ESKD and 2 (3%) died. CONCLUSION: Almost half of adults with primary FSGS achieved sustained remission with steroids and immunosuppressants and consequently exhibited excellent long-term outcome.  DOI: 10.52547/ijkd.6815.

Molecular Modelling of Optical Biosensor Phosphorene-Thioguanine for Optimal Drug Delivery in Leukemia Treatment.

Thioguanine is an anti-cancer drug used for the treatment of leukemia. However, thioguanine has weak aqueous solubility and low biocompatibility, which limits its performance in the treatment of cancer. In the present work, these inadequacies were targeted using density functional theory-based simulations. Three stable configurations were obtained for the adsorption of thioguanine molecules on the phosphorene surface, with adsorption energies in the range of -76.99 to -38.69 kJ/mol, indicating physisorption of the drug on the phosphorene surface. The calculated bandgap energies of the individual and combined geometries of phosphorene and thioguanine were 0.97 eV, 2.81 eV and 0.91 eV, respectively. Owing to the physisorption of the drug molecule on the phosphorene surface, the bandgap energy of the material had a direct impact on optical conductivity, which was significantly altered. All parameters that determine the potential ability for drug delivery were calculated, such as the dipole moment, chemical hardness, chemical softness, chemical potential, and electrophilicity index. The higher dipole moment (1.74 D) of the phosphorene-thioguanine complex reflects its higher biodegradability, with no adverse physiological effects.

Benzocaine: Review on a Drug with Unfold Potential.

Benzocaine is well-known for its role as an anesthetic agent and largely used in oral ulcers, ear pain and dental complications. Along with lidocaine and other local anesthetics, benzocaine has marked it as an anesthetic agent in surgical procedures and as Na+ channels blocker, as well. Analogues of benzocaine have been found to possess biological potentials including antibacterial, antifungal and anti-cancer. Some derivatives were found to have conspicuous action against tuberculosis. The current review focuses to explore the century-long potential of the molecule and its analogs that have appeared in the literature. Furthermore, highlighting the biological potential of benzocaine and its analogues shall open-up new dimensions of future research to design more potent analogues.

Antioxidant activity of Vitis vinifera, Punica granatum, Citrus aurantium and Opuntia ficus indica fruits cultivated in Algeria.

Four edible fruits from Vitis vinifera, Punica granatum, Citrus aurantium and Opuntia ficus indica from Algeria were analyzed in order to determine the total polyphenol, total flavonoid and flavonol contents using classical spectrophotometric methods. The antioxidant activity was established by three different single-electron-transfer-based assays (ABTS radical cation, FRAP, and DPPH assays) and one hydrogen-atom-transfer based assay (ORAC). Among the four fruits tested, the Vitis vinifera hydroalcoholic extract showed the highest antioxidant capacity with all methods. The results indicated that the antioxidant activity and the total phenolic content of the selected plants are significantly different (p < 0.001).

Auto-Amputated Ovary Presenting as Abdominal Mass in an Infant.

Among female infants, a mass in the abdomen carries a large number of differential diagnoses. Arelatively uncommon condition is ovarian cyst, which may be encountered among such patients. Even more rare condition is auto-amputation of ovary. We herein, present a case of a female infant who presented as abdominal mass and turned out to be autoamputation of right ovary attached to mesentery of intestine. It was excised successfully and the patient is doing well at 3 years follow-up.

Acute tubulointerstitial nephritis/drug induced acute kidney injury; an experience from a single center in Pakistan.

INTRODUCTION: There is no information in literature specifically on the prevalence and clinicopathological characteristics of acute tubulointerstitial nephritis/drug induced acute kidney injury (AKI) from Pakistan. OBJECTIVES: We aim to report a series of cases from patients developing AKI after exposure to some medications or finding of interstitial nephritis on histopathology. PATIENTS AND METHODS: This is an observational study of patients identified as having AKI after exposure to medications. AKI was defined according to RIFLE criteria and all patients fell from risk to loss category on arrival. On ultrasonography, all patients had normal size non-obstructed kidneys. Renal biopsy findings were consistent with tubule interstitial nephritis. RESULTS: Mean age of patients was 36.41 ± 17.40 years. Among total of 155, 80 were male and 75 female. Regarding drugs, most common was exposure to aminoglycoside in 34 (22%) followed by use of non-steroidal anti-inflammatory analgesics in 28, contrast induced agents in 11. Renal biopsy was performed in 58 patients. In half of these, insulting agent was not known and in rest either multiple medications were ingested or there was denial to substance use or recovery was delayed despite discontinuation of responsible medication. Renal replacement therapy was required on arrival in 119/155 (hemodialysis = 115, peritoneal dialysis = 4) cases. Complete renal recovery was observed in 71%, while 7.7% expired during acute phase, partial renal recovery was seen in 15% and 5% disappeared after first discharge from the hospital. CONCLUSION: Tubulointerstitial nephritis may occur with many drugs of common use. Early and intensive efforts must be made to consider and then timely correct the injury to the kidney.

Anti-HIV cytotoxicity enzyme inhibition and molecular docking studies of quinoline based chalcones as potential non-nucleoside reverse transcriptase inhibitors (NNRT).

A series of fourteen (A1 - A14) qunioline based chalcones were screened for reverse transcriptase inhibitors (RT) and found potentially active against RT. Bioassay, theoretical and dockings studies with RT (the enzyme required for reverse transcription of viral RNA) results showed that the type and positions of the substituents seemed to be critical for their inhibition against RT. The bromo and chloro substituted chalcone displayed high degree of inhibition against RT. The A4 andA6 showed high interaction with RT, contributing high free binding energy (ΔG -9.30 and -9.13kcal) and RT inhibition value (IC50 0.10µg/ml and 0.11µg/ml).

Spectrum of glomerular diseases causing acute kidney injury; 25 years experience from a single center.

INTRODUCTION: Acute kidney injury (AKI) is common in nephro-urological practice. Its incidence, prevalence and etiology vary widely, mainly due to variations in the definitions of AKI. OBJECTIVES: We aim to report the spectrum of glomerular diseases presenting as AKI at a kidney referral center in Pakistan. PATIENTS AND METHODS: An observational cohort of patients identified as having AKI which was defined according to RIFLE criteria, with normal size, non-obstructed kidneys on ultrasonography, along with active urine sediment, edema and new onset hypertension. RESULTS: From 1990 to 2014, 236 cases of AKI secondary to acute glomerulonephritis (AGN) registered at this institution. Mean age of patients was 27.94± 12.79 years and M:F ratio was 0.77:1. Thirty percent patients revealed crescents on renal biopsy. AGN without crescents was seen in 33.05% of cases. Postinfectious GN was found in 14.4%, lupus nephritis in 8.5% and mesangiocapillary GN in 3.4% cases. Renal replacement therapy (RRT) required in 75.84% patients. Pulse steroids were given in 45.33% cases followed by oral steroids. Pulse cyclophoshphamide was given in 23.7% cases and plasmapheresis was used in 3.38% cases. Complete recovery was seen in 44%, while 11.44% died during acute phase of illness. About 19.49 % developed chronic kidney disease (CKD) and 25.84% were lost to long- term follow-up. CONCLUSION: Although glomerular diseases contribute only 4.19 % of total AKI at this center, morbidity associated with illness and its treatment is more marked than other AKI groups. Another notable factor is late referral of these patients to specialized centers resulting in undesirable outcome.

Duplication Cyst Presenting as Hydrocoele in a Child.

Enteric duplication cyst can occur anywhere in Gastrointestinal Tract (GIT), from oropharynx to rectum. Their presentation depends upon the portion of GIT involved. The most common site of GIT involved is small intestine, in 50% of cases. Small intestinal duplication cyst usually present with abdominal pain or mass and rarely as intussusception, volvulus or small bowel obstruction. It may also present very rarely as inguinal hernia of which only 2 cases have been reported yet. We report a 3 years child presenting as hydrocoele of the cord which turned to be duplication cyst which is very rare presentation.

Acute renal failure in diabetes mellitus.

OBJECTIVE: To study the causes and outcome of Acute renal failure (ARF) in diabetes mellitus. METHODS: This prospective study was conducted at nephrology unit of SIUT Karachi, Pakistan from November 2012 to May 2013. All adult patients with known underlying diabetes presenting with suspected ARF were included in the study. The treatment options were conservative and dialysis. Renal biopsy was performed in selected patients. All patients were followed for a period of six weeks for outcome of renal failure i.e. recovery, dialysis dependency and death. RESULTS: A total of 95 patients with suspected ARF were enrolled during this period. We found sepsis as the single most common factor causing ARF in 66 (69.5%) patients and the most common focus of infection was found to be urinary tract in 47 (71.2%) patients. Other factors leading to ARF included volume depletion in 19 (20%), cardio renal in 13 (13.7%), acute glomerulonephritis in 3 (3.15%) and contrast exposure in 2 (2.1%) patients. In all 72 (75.8%) patients required dialysis, while 23 (24.2%) were managed conservatively. Eventually 62 (67.39%) patients recovered, 14 (15.21%) became dialysis dependent, and 16 (17.39%) died. Among those who expired, all underwent dialysis and sepsis was the leading cause of death in 13 (81.25%) patients. CONCLUSION: Infection, especially of urinary tract is the leading cause of ARF in Diabetics. Outcome is favourable in those who dot require dialysis.

Mitochondrial Targeted Antioxidant in Cerebral Ischemia.

There has been much evidence suggesting that reactive oxygen species (ROS) generated in mitochondria during cerebral ischemia play a major role in programming the senescence of organism. Antioxidants dealing with mitochondria slow down the appearance and progression of symptoms in cerebral ischemia and increase the life span of organisms. The mechanisms of mitochondrial targeted antioxidants, such as SKQ1, Coenzyme Q10, MitoQ, and Methylene blue, include increasing adenosine triphosphate (ATP) production, decreasing production of ROS and increasing antioxidant defenses, providing benefits in neuroprotection following cerebral ischemia. A number of studies have shown the neuroprotective role of these mitochondrial targeted antioxidants in cerebral ischemia. Here in this short review we have compiled the literature supporting consequences of mitochondrial dysfunction, and the protective role of mitochondrial targeted antioxidants.

Prevalence and risk factors for early chronic allograft nephropathy in a live related renal transplant program.

BACKGROUND: Chronic allograft nephropathy (CAN) is a common cause of delayed allograft failure throughout the world. Its prevalence and risk factors vary depending on a number of factors. There is little information on the prevalence and risk factors for early CAN in live related renal transplant patients. OBJECTIVES: We aimed to determine the prevalence and the risk factors of early CAN in our setup. PATIENTS AND METHODS: The study was conducted at Sindh Institute of Urology & Transplantation (SIUT), Karachi, from 2002 to 2005 on patients who had live related kidney transplantation and underwent at least one allograft biopsy within 18 months of transplantation. The biopsies were performed and prepared in accordance with established indications and guidelines. The Banff 97 classification and its updates were used to diagnose and categorize the biopsy pathology. Patients were divided into two groups depending on the presence or absence of CAN on biopsies. Following parameters were compared among the groups: age, sex, human leukocyte antigen (HLA) match, immunosuppression used, acute rejection (AR) episodes, urinary tract infections (UTIs), viral infections, cyclosporine levels, early and late graft function monitored by serum creatinine. RESULTS: A total of 164 patients fulfilled the study inclusion criteria. The mean age of recipients and donors was relatively young. The majority of the donors were siblings. The overall prevalence of CAN was 25.6% (42/164), between 3 and 18 months post transplantation. The median time to the appearance of CAN was 9 months post-transplant. The prevalence of CAN increased as post-transplant duration increased. In 39 (92.8%) subjects, CAN was detected on the second or subsequent graft biopsy. Only 3 (7.2%) patients showed CAN on the first graft biopsy. The majority of cases belonged to moderate degree or grade II CAN. The mean serum creatinine values were higher in the CAN group at the time of discharge and all times post-transplantation. CONCLUSIONS: In conclusion, the results show that serum creatinine at the time of discharge is a useful predictor of later development of chronic changes in the allograft. Further studies are needed to identify the risk factors for the early development of chronic changes in living related renal transplant program.

Optical analysis of hafnium oxide-aluminum multilayer structures for transparent heat mirrors.

We report on HfO2/Al/HfO2 multilayer thin films for heat mirror applications prepared on corning glass substrates by electron beam evaporation. Films fabricated at a substrate temperature of 100 °C show nano-polycrystals of HfO2 embedded in a disordered lattice according to X-ray diffraction results. Atomic force microscopy revealed that HfO2/Al/HfO2 layers possess smooth surface that is appropriate for optical heat mirror applications. Study of optical properties by UV-Visible spectrophotometer demonstrated that transmittance of HfO2/Al/HfO2 device was decreasing from UV to VIS and then slightly increasing in the NIR regions, with an opposite trend followed by reflectance. Optical constants i.e. refractive index, extinction coefficient, band gap energy, Urbach energy has also been calculated. The optical band gap and Urbach energy are found to be 4.34 eV and 3.164 eV, respectively. The collective oscillation energy loss for heat mirrors applications are also observed.

Renal transplant in a tuberous sclerosis patient with bilateral giant renal angiomyolipomas and concurrent renal carcinoma.

Co-existence of angiomyolipoma (AML) and renal cell carcinoma (RCC) in the same tumor mass is very rare and only eight cases have been reported. We present a case of a young female with tuberous sclerosis complex (TSC) with bilateral huge renal AMLs. Both tumors were removed, one of which revealed co-incidental RCC. She was subsequently successfully transplanted a kidney from her brother and is maintaining normal graft function eight months post-transplant. No recurrence or metastases of RCC has been detected till the last follow-up.