Therapeutic effect of cycloserine combined with anti-tuberculosis drugs in the treatment of multidrug-resistant tuberculosis

Purpose: The present study analyzes the comprehensive therapeutic effect of cycloserine, in combination with anti-tuberculosis drugs using chest X-ray and chest CT (computed tomography) scan techniques. Methods: A total of 90 patients, diagnosed with multidrug resistant tuberculosis (MDR TB) were subjected to chest x-ray and CT scan before and after treatment in the two groups. Different views such as sagittal, coronal, lung window and multiplanar imaging of mediastinal window were taken. Some parameters such as case detection rate (CDR) in chest X-ray and CT scan and comprehensive curative effect were observed in two groups. Further, the changes in chest CT signs in addition to absorption of focus, cavity closure and changes in CT extra pulmonary signs were also observed. Results: The clinical profile of the patients and the course of disease were statistically insignificant (p > 0.05). Total effectiveness rate and case detection rate (CDR) values exhibited a significant difference between the groups (p < 0.05). Lung consolidation, nodules and cavities significantly improved in both groups before and after the treatment (p < 0.05). Both groups showed significant improvements in extrapulmonary signs in CT scan (p < 0.05) after the treatment. Conclusion: Based on the study outcomes, the CT scan method has good potentials for diagnosing and treating MDR TB at the early stages. Further, it can clarify the signs and outcomes of the disease at early stages, thus providing the medical fraternity a great opportunity to cure the disease.

Effect of angiotensin converting enzyme gene polymorphism on patients with in-stent restenosis after percutaneous coronary intervention

Purpose: To evaluate the association between common single nucleotide polymorphisms (SNPs) in angiotensin converting enzyme (ACE) gene and the risk of in-stent restenosis (ISR) and/or the response to angiotensin converting enzyme inhibitor ACEI in individuals with stable coronary artery disease (CAD) after stent implantation. Methods: The total population of this study consisted of 200 Egyptian individuals divided into 2 groups - in-stent restenosis (ISR) and non ISR group). Genomic DNA was withdrawn from EDTA whole blood applying a spin column approach and ACE gene insertion/deletion (I/D) polymorphisms were determined by polymerase chain reaction (PCR). Results: Carriers of allele D of ACE gene were significantly more liable to ISR occurrence. However, carriers of allele I were significantly more liable to ISR occurrence after administration of ACEI. There is a negative interaction between DD genotype of ACE gene and ACEI administration on ISR after percutaneous coronary intervention (PCI). However, there is a positive interaction between II and ID genotype of ACE gene and ACEI administration on ISR after PCI with bare metal stents (BMS). Conclusion: It is beneficial to implement ACEI in therapeutic regimen in individuals with ID or II genotypes of ACE gene, especially with BMS implementation.

Neuroprotective effects of crude extract of Crataegus songarica on a rat model of traumatic brain injury

Purpose: To investigate the protective effect of Crataegus songarica extract (CSCE) against traumatic brain injury (TBI) in rats, and the underlying mechanism of action. Methods: A rat model of TBI was established via tracheal intubation procedure, and the rats were treated with graded doses of CSCE. Neuronal survival was determined by Nissl staining, while neuronal apoptosis was measured using TUNEL-staining. Neurological impairments were determined based on neurological severity score (NSS). Results: Treatment of TBI rats with CSCE enhanced neuronal survival and decreased TUNEL-positive cell fraction in the brain cortex. The treatment prevented elevation of NSS and suppressed mRNA and protein expression levels of IL-6 and TNF-α in brain cortex. Moreover, CSCE treatment prevented TBI-mediated suppression of activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx), and attenuated hydrogen peroxide (H2O2) levels in TBI rat brain cortex. Treatment of TBI rats with CSCE down-regulated NF-κB expression, increased Nrf2 expression and up-regulated mRNA expressions of heme oxygenase 1 (HO-1) and quinine oxidoreductase 1 (NQO-1). Conclusion: These results suggest that CSCE prevents TBI-mediated reduction in neuronal survival and inhibits brain cortical neuronal death in rats. It improves NSS and inhibits inflammatory response via activation of Nrf2 pathway and targeting of NF-κB expression. Therefore, CSCE is a potential therapeutic agent for TBI.

Rapid screening and characterization of caffeic acid metabolites in rats by UHPLC-Q-TOF mass spectrometry

Purpose: To determine the metabolism of caffeic acid in rats. Methods: Sprague-Dawley rats were intragastrically administered caffeic acid in saline suspension, and biological samples collected. After sample pretreatment by solid phase extraction, ultra-high performance liquid chromatography combined with quadrupole-time of flight mass spectrometry system (UHPLC-Q-TOF-MS/MS) was established to rapidly screen and characterize caffeic acid metabolites in rats. Waters HSS T3 UPLC chromatographic column (2.1 mm × 100 mm, 1.7 μm) was applied for the gradient elution with aqueous solution of formic acid (A)-acetonitrile (B). Mass spectral data for the biological samples in electrospray positive and negative ion modes were collected and analyzed by SCIEX OS 1.3 workstation. Results: Based on their precise molecular weights and multistage mass spectrometry cleavage information, caffeic acid and 21 metabolites in vivo were identified. The results demonstrate that the biotransformation of caffeic acid in vivo was mainly achieved via hydrogenation, hydroxylation, methylation, sulfonation, glucuronidation, acetylation, and composite reactions. Conclusion: The metabolites and metabolic pathways of caffeic acid in rats have been rapidly elucidated, and its potential pharmacodynamics forms have been clarified. This provides a valuable and meaningful reference for the study of caffeic acid metabolites, biological activities, and its medicinal material basis in vivo.

Studies of the pharmacokinetics of morroniside and loganin in rat after oral administration of raw and wine-processed Corni fructus by UPLC-QqQ-MS/MS

Purpose: To study the pharmacokinetics of morroniside (MR) and loganin (LG) in rats after oral administration of raw and wine-processed Corni fructus by UPLC-QqQ-MS/MS. Methods: Arctiin (AT) was used as internal standard, and the plasma or tissue samples were extracted twice using ethyl acetate. Electrospray ionization (ESI) negative ion mode was used, and the multiple reaction monitoring mode (MRM) was set in acquisition mode. The extraction and detection method is supported by selectivity, sensitivity, precision, accuracy, stability, extraction, recovery and matrix effect. The non-atrioventricular model of das2.0 software was used to calculate the pharmacokinetic parameters. Results: The absorption rate of MR (PTmax=0.092) and LG (PTmax=0.092) in Corni Fructus after wine-processing was faster in rats. The mean residence time was longer, and distribution of MR (PMRT0~t = 0.294) and LG (PMRT0~t = 0.000) in wine-processed Corni Fructus group increased in liver and kidneys. Conclusion: The proposed method has been successfully validated and is suitable for studying the pharmacokinetics of the two analytes in rats.

A study on the utilization of rice husk as a biosorbent material for Cr (VI) removal from industrial effluent

Purpose: To study Cr (VI) removal from waste water using chromium-resistant bacterial strains in combination with rice husk. Methods: Two strains of Exiguobacterium sp. resistant to chromium (VI) were applied in the present work. Rice husk (RH) was used as an agricultural waste for Cr (VI) removal. The elimination of Cr from the husk was chemically facilitated using hydrochloric, sulphuric and citric acids, as well as formaldehyde and potassium dihydrogen phosphate Investigation of optimum physical factors such as pH, temperature, shaking speed and biomass concentration on Cr (VI) removal was carried out using citric acid-processed rice husk alone, and in combination of bacterial strains. Fourier transform infra-red (FTIR) spectroscopy was performed to determine the contributions of different functional groups involved in Cr (VI) binding. Scanning electron microscopy (SEM) of treated and untreated RH was also performed. Results: Citric acid-processed RH was most effective in the removal of chromate (97.3 %). The two bacterial strains combined with rice husk proved highly efficient in Cr (VI) removal from sterile and non-sterile industrial effluents. FTIR spectra showed the involvement of esters, amines and aliphatic functional groups in Cr (VI) binding, while SEM displayed the damaging effects of Cr (VI) on the surface of RH; however, bacterial inoculation minimized the damage. Conclusion: Exopolysaccharides from Exiguobacterium strains and citric acid-processed rice husk demonstrated high efficiency for Cr (VI) removal. Hence, RH with these bacterial strains are potential biosorbents for control of heavy metal contamination arising from industrial effluents.

Determination of the heavy metal contents of frequently used herbal products in Pakistan

Purpose: To determine the heavy metal content of selected local and international herbal medicines sold for the treatment of various diseases in Pakistan. Methods: The different dosage forms of herbal medicines assessed were crude forms of syrups, gel, capsule, powder and tonic. Wet digestion method was used to prepare the herbal samples using nitric acid, and then analyzed for arsenic (As), cadmium (Cd), lead (Pb) and mercury (Hg), using MHS-15 mercury/hydride system and flame atomic absorption spectrometry (FAAS). Results: The investigated results displayed the Arsenic level (0.00 ppm to 0.580 ppm); Cadmium (0.001 ppm to 0.006 ppm); Lead (0.00 ppm to 1.078 ppm) and Mercury (0.001 ppm to 0.012 ppm). All results were found below the permissible limit of acceptability intake of the World Health Organization (WHO) and American Herbal Products Association (AHPA). The pH of the samples were in the range of 1.52 to 6.99. Conclusion: The findings reveal that the investigated herbal products available in Pakistan are safe with reference to heavy metals, and considered non-toxic for human consumption.

Protective effect of Rhus chinensis Mill. extract against liver cirrhosis in rats

Purpose: To study the effect of Rhus chinensis Mill. extract (RCME) on diethylnitrosamine (DEN)-induced liver cirrhosis in rats. Methods: RCME was obtained by extracting the dried Rhus chinensis Mill. in water. Liver cirrhosis rat model was prepared by injecting with DEN once a week for 8 weeks. After 8th-week of RCME treatment, biochemical index and oxidative stress were determined in DEN-induced liver cirrhosis in rats. Results: Compared with model group, plasma concentrations of alanine transaminase (ALT, 125.3 ± 4.1 U/L) and aspartate aminotransferase (AST, 152.4 ± 3.5 U/L) decreased significantly (p < 0.01) in the 8th week. Rhus chinensis Mill. extract (RCME) significantly decreased malondialdehyde (MDA, 0.18 ± 0.02 umol/L) and superoxide dismutase (SOD, 0.76 ± 0.05 U/mg protein) in DEN-induced liver cirrhosis in rats (p < 0.01) when compared with model group. Conclusion: RCME protects against diethylnitrosamine-induced liver cirrhosis in rats. However, further investigations are required to ascertain the plant extract’s suitability for the clinical management of liver cirrhosis.

Molecular docking study on columbin isolated from Tinospora cordifolia as a cholinesterase inhibitor

Purpose: To investigate the acetylcholinesterase (AChE) inhibitory potential of columbin and also to assess its binding affinity against AChE protein. Methods: Crystals of columbin were isolated from the ethyl acetate fraction of Tinospora cordifolia using column chromatography and its structure was determined using x-ray crystallography. Ellman colorimetric assay was used to determine the AChE inhibitory effect in vitro while molecular docking was performed using the MOE 2015.010 software. The selected protein data bank (PDB) was modeled using PDB ID: 10CE (pacific electric ray). Results: The crystal and structure refinement data of columbin were: C20H22O6, Orthorhombic, P212121, a = 7.4951(2) Å (α = 90°), b = 11.6451(3) Å (β = 90°), c = 19.5882(5) Å (γ = 90°), V=1709.68(8) Å3, Z = 4, Density (calculated) = 1.392 Mg/m3, absorption coefficient = 0.851 mm-1, goodness-of-fit on F2 =1.091, T = 100(2) K. Columbin demonstrated good AChE inhibitory effect with half-maximal inhibitory concentration (IC50) of 1.2993 ± 0.17 mg/mL. Molecular docking data revealed that it exhibited hydrophobic and hydrogen bonding interactions with the surrounding residues, and this accelerated complexation between the ligands and the active site of the enzyme. Conclusion: Columbin may be useful in the management of neurodegenerative conditions such as Alzheimer’s disease.

Aqueous Allium sativum (garlic) extract ameliorated CdCl2- induced alterations in blood formation and spermatogenesis in albino rats

Purpose: To investigate the ameliorative effect of aqueous garlic extract (AGEx) on cadmium chloride (CdCl2-induced) alterations in the blood and testicles of rats. Methods: A total of 24 male rats (160 - 200 g), randomly assigned into 4 groups (A - D; n = 6), were used to investigate the claimed protective effect of AGEx on blood and spermatogenic tissues following CdCl2-intoxication in albino rats. The rats in Group A served as controls and were given 5 mg/mL of deionized water. Group B rats were given 300 mg/kg of AGEx. Group C rats were given 2 mg/kg of CdCl2. Rats in Group D first received 2 mg/kg of CdCl2, and 300 mg/kg of AGEx 2 h later. All treatments were done every 48 h for a period of six weeks. Results: CdCl2 administration to group C rats reduced (p < 0.05) haematocrit value (PCV), concentration of haemoglobin (Hb), red cells count (RBC), total leucocytes count (tWBC), eosinophil, neutrophil, testicular weights and sperm reserves; but elevated (p < 0.05) lymphocytes count compared with the controls. AGEx 300 mg/kg in group D rats significantly reversed (p < 0.05) the altered parameters compared with the controls. Conclusion: The results demonstrate that administration of aqueous Allium sativum (garlic) extract to male rats enhances spermatogenesis, and ameliorates testicular and haematological alterations induced by cadmium poisoning. Therefore, the spermatogenic principle in AGEx is a potential candidate for the clinical management of male infertility.