Administration of Vaccine Preservative Thimerosal Produces Impairment in Rat Liver

Abstract The present research was planned to analyze the toxic effects of thimerosal on rat liver. Mercury and mercury compounds are universally known toxicants for animals and humans. Thimerosal is widely used in the vaccines as a preservative which contains 49.6% mercury. Twenty-four adult male albino rats were distributed into four groups (n=6). The first group was considered as a control group. While, second, third and fourth groups were intoxicated with 0.5, 10 and 50 µg/kg thimerosal (i.m.) respectively. After 30 days, rats were slaughtered to analyze the liver tissues. The results of the experiment exposed that thimerosal instigated significant (p<0.05) increase in alanine transaminase (ALT), alkaline phosphatase (ALP) and aminotransferase (AST) levels. Catalase (CAT), superoxide dismutase (SOD), peroxidase (POD) activities and Glutathione (GSH) and protein levels were significantly (p<0.05) reduced. Furthermore, significant increases in Hydrogen peroxide (H2O2), thiobarbituric acid reactive substances (TBARS) level and DNA damage was observed. Histopathological study revealed severe damages, e.g. fatty alterations, deterioration of lobular structure and degeneration of nuclei in hepatic tissues of thimerosal treated rats. Results of present investigation revealed that thimerosal induces hepatotoxicity at different levels.

Therapeutic potential of medicinal plants against Leishmaniasis: a public healh concern / Potencial terapeútico de plantas medicinales contra la Leishmaniasis: un problema de salud pública

Leishmaniasis is an important disease affecting global public health which is spread by sand fly having different species. Various chemical drugs are used to treat and control Leishmaniasis including pentavalent antimonials, antimicrobial and antibiotics. Due to emergence of drug resistance, these therapeutic options are losing effectiveness in attaining success. Furthermore, these drugs are expensive and have toxic effects on liver and kidneys. There has been an emerging interest and excellent response by using plant based drugs and extracts to control Leishmaniasis. Different medicinal plants including Glycyrrhiza glabra, Allium sativum, Peganum harmala and Nigella sativa have shown excellent anti-leishmanial activity. Therefore, medicinal plants can help in effective drug development against Leishmaniasis diseases in both animals and humans which will be safer and health protective.

La Leishmaniasis es una enfermedad importante que afecta la salud pública mundial y que es transmitida por las moscas de la arena, que tienen diferentes especies. Se utilizan varios medicamentos químicos para tratar y controlar la Leishmaniasis, incluidos los antimoniales pentavalentes, antimicrobianos y antibióticos. Debido a la aparición de resistencia a los medicamentos, estas opciones terapéuticas están perdiendo eficacia para lograr el éxito. Además, estos medicamentos son costosos y tienen efectos tóxicos en hígado y riñones. Ha habido un interés emergente y una excelente respuesta mediante el uso de extractos y medicamentos a base de plantas para controlar la Leishmaniasis. Diferentes plantas medicinales como Glycyrrhiza glabra, Allium sativum, Peganum harmalay Nigella sativahan mostrado una excelente actividad anti-leishmanial. Por lo tanto, las plantas medicinales pueden ayudar en el desarrollo de fármacos eficaces contra las enfermedades de la leishmaniasis tanto en animales como en seres humanos, lo que será más seguro y proteja la salud.

Molecular characterization and expression pattern analysis of a novel stress-responsive gene ‘BeSNAC1’ in Bambusa emeiensis

NAC transcription factors (TFs) are master regulators of environmental stresses exerting a crucial role in plant growth and development. However, the studies on NAC TFs from Bambusa emeiensis are scarce. In this investigation, a novel gene from B. emeiensis encoding NAC protein was cloned and characterized. The gene was isolated based on the amino acid sequence data of stress-responsive SNAC1 of rice, named ‘BeSNAC1 (accession no. MG763922)’. The full-length sequence of 1681 bp was found to contain an open-reading frame of 912 bp that encode a protein of 303 amino-acid residues. The multiple protein sequence alignments unveiled that BeSNAC1 contains a typical NAC domain. Additionally, the phylogenetic analysis showed that the corresponding protein belonged to the SNAC group, as it cladded with SNAC1, HvSNAC1, TaNAC2, SbSNAC1 and ZmSNAC1 proteins. Transactivation and subcellular localization assay disclosed that BeSNAC1 is a transcriptional activator localized in the cell nucleus.Moreover, the time-dependent expression pattern of BeSNAC1 was profiled under abscisic acid (ABA), polyethylene glycol 6000 (PEG-6000), NaCl, H2O2 and Na2SO4 treatments via a quantitative real-time polymerase chain reaction. The results revealed that the expression of BeSNAC1 was significantly upregulated in all treatments, a significant difference was observed under H2O2, NaCland ABA (P 0.001) and PEG and Na2SO4 (P < 0.01) treatments, respectively. Conclusively, our findings provide evidence that ‘BeSNAC1’ is a nuclear protein that might act as part of the transcription regulation complex and is involved in the ABA signalling pathway and abiotic stress tolerance mechanisms in B. emeiensis.

Incidence of deep venous Thrombosis in Laparoscopic Cholecystectomy without Thromboprophylaxis

Objective: To determine the incidence of clinically detectable deep venous thrombosis [DVT] in patients undergoing laparoscopic cholecystectomy without a standard DVT prophylaxis regimen

Study Design: Prospective observational study

Place and Duration of Study: All the patients included in the study underwent laparoscopic cholecystectomy from Nov 2014 to Nov 2016 in Hepatobiliary department Pak Emirates Military Hospital Rawalpindi under general anaesthesia

Material and Methods: The study was carried out on 723 patients undergoing laparoscopic cholecystectomy. Data was collected on a specially designed proforma. Quantitative D-dimers and 3 risk stratification [Wells score] for deep venous thrombosis was done 24 hrs preoperatively 24 hrs, 72 hrs and 14 days postoperatively

Results: The study population comprised of 723 patients. Twenty seven patients were converted to undergo open cholecystectomy and were excluded from the study. Forteen patients were lost to follow-up. 03 pts with preop high probability of DVT were excluded from further postoperative screening. During postoperative screening, 05 out of 679 pts had a Wells score of more than 03, which showed a high probability of DVT in these patients. Out of these 05 pts, four had raised D-dimers as well. For definitive diagnosis, all these 05 patients underwent duplex scan, which confirmed deep venous thrombosis

Conclusion: We conclude that there is no significant risk of DVT after laparoscopic cholecystectomy. Thromboprophylaxis is not recommended in patients undergoing elective laparoscopic cholecystectomy without any risk factors of DVT. Preoperative risk stratification for DVT and D-dimers are effective screening tools for pts undergoing laparoscopic cholecystectomy

Anticholinesterse and antioxidant investigations of crude extracts, subsequent fractions, saponins and flavonoids of atriplex laciniata L: potential effectiveness in Alzheimer's and other neurological disorders

BACKGROUND: Atriplex laciniata L. was investigated for phenolic, flavonoid contents, antioxidant, anticholinesterase activities, in an attempt to explore its effectiveness in Alzheimer's and other neurological disorders. Plant crude methanolic extract (Al.MeF), subsequent fractions; n-hexane (Al.HxF), chloroform (Al.CfF), ethyl acetate (Al.EaF), aqueous (Al.WtF), Saponins (Al.SPF) and Flavonoids (Al.FLVF) were investigated for DPPH, ABTS and H2O2 free radical scavenging activities. Further these extracts were subjected to acetylcholinesterase (AChE) & butyrylcholinesterase (BChE) inhibitory activities using Ellman's assay. Phenolic and Flavonoid contents were determined and expressed in mg Gallic acid GAE/g and Rutin RTE/g of samples respectively. RESULTS: In DPPH free radicals scavenging assay, Al.FLVF, Al.SPF and Al.MeF showed highest activity causing 89.41 ± 0.55, 83.37 ± 0.34 and 83.37 ± 0.34% inhibition of free radicals respectively at 1 mg/mL concentration. IC50 for these fractions were 33, 83 and 82 µg/mL respectively. Similarly, plant extracts showed high ABTS scavenging potential, i.e. Al.FLVF (90.34 ± 0.55), Al.CfF (83.42 ± 0.57), Al.MeF (81.49 ± 0.60) with IC50 of 30, 190 and 70 µg/ml respectively. further, H2O2 percent scavenging was highly appraised in Al.FLVF (91.29 ±0.53, IC50 75), Al.SPF (85.35 ±0.61, IC50 70) and Al.EaF (83.48 ± 0.67, IC50 270 µg/mL). All fractions exhibited concentration dependent AChE inhibitory activity as; Al.FLVF, 88.31 ± 0.57 (IC50 70 µg/mL), Al.SPF, 84.36 ± 0.64 (IC50 90 µg/mL), Al.MeF, 78.65 ± 0.70 (IC50 280 µg/mL), Al.EaF, 77.45 ± 0.46 (IC50 270 µg/mL) and Al.WtF 72.44 ± 0.58 (IC50 263 µg/mL) at 1 mg/mL. Likewise the percent BChE inhibitory activity was most obvious in Al.FLVF 85.46 ± 0.62 (IC50 100 µg/mL), Al.CfF 83.49 ± 0.46 (IC50 160 µg/mL), Al.MeF 82.68 ± 0.60 (IC50 220 µg/mL) and Al.SPF 80.37 ± 0.54 (IC50 120 µg/mL). CONCLUSIONS: These results stipulate that A. laciniata is enriched with phenolic and flavonoid contents that possess significant antioxidant and anticholinestrase effects. This provide pharmacological basis for the presence of compounds that may be effective in Alzheimer's and other neurological disorders.

Antioxidant and anticholinesterase investigations of Rumex hastatus D. Don: potential effectiveness in oxidative stress and neurological disorders

BACKGROUND: Rumex species are traditionally used for the treatment of neurological disorders including headache, migraine, depression, paralysis etc. Several species have been scientifically validated for antioxidant and anticholinestrase potentials. This study aims to investigate Rumex hastatus D. Don crude methanolic extract, subsequent fractions, saponins and flavonoids for acetylcholinestrase, butyrylcholinestrase inhibition and diverse antioxidant activities to validate its folkloric uses in neurological disorders. Rumexhastatus crude methanolic extract (Rh. Cr), subsequent fractions; n-hexane (Rh. Hex), chloroform (Rh. Chf), ethyl acetate (Rh. EtAc), aqueous fraction (Rh. Aq), crude saponins (Rh. Sp) and flavonoids (Rh. Fl) were investigated against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) at various concentrations (125, 250, 500,1000 µg/mL) using Ellman's spectrophotometric analysis. Antioxidant potentials of Rh. Sp and Rh. Fl were evaluated using DPPH, H2O2 and ABTS free radical scavenging assays at 62.5, 125, 250, 500, 1000 µg/mL. RESULTS: All the test samples showed concentration dependent cholinesterase inhibition and radicals scavenging activity. The AChE inhibition potential of Rh. Sp and Rh. Fl were most prominent i.e., 81.67 ± 0.88 and 91.62 ± 1.67 at highest concentration with IC50 135 and 20 µg/mL respectively. All the subsequent fractions exhibited moderate to high AChE inhibition i.e., Rh. Cr, Rh. Hex, Rh. Chf, Rh. EtAc and Rh. Aq showed IC50 218, 1420, 75, 115 and 1210 µg/mL respectively. Similarly, against BChE various plant extracts i.e., Rh. Sp, Rh. Fl, Rh. Cr, Rh. Hex, Rh. Chf, Rh. EtAc and Rh. Aq resulted IC50 165,175, 265, 890, 92, 115 and 220 µg/mL respectively. In DPPH free radical scavenging assay, Rh. Sp and Rh. Fl showed comparable results with the positive control i.e., 63.34 ± 0.98 and 76.93 ± 1.13% scavenging at 1 mg/mL concentration (IC50 312 and 104 µg/mL) respectively. The percent ABTS radical scavenging potential exhibited by Rh. Sp and Rh. Fl (1000 µg/mL) were 82.58 ± 0.52 and 88.25 ± 0.67 with IC50 18 and 9 µg/mL respectively. Similarly in H2O2 scavenging assay, the Rh. Sp and Rh. Fl exhibited IC50 175 and 275 µg/mL respectively. CONCLUSION: The strong anticholinesterase and antioxidant activities of Rh. Sp, Rh. Fl and various fractions of R. hastatus support the purported ethnomedicinal uses and recommend R. hastatus as a possible remedy for the treatment of AD and neurodegenerative disorders.

Fabrication and Characterization of Gliclazide Loaded Microcapsules

This study aimed to formulate, characterize and evaluate the Gliclazide (GLZ) microcapsules prepared with sodium alginate, guar gum and pectin in different ratios by ionotropic-gelation method. The microcapsules were evaluated against different parameters such as particle size and shape, Carr's index, Hausner's ratio, rheological studies and drug release kinetics. Fourier Transform Infra Red (FTIR) and Differential Scanning Calorimetric (DSC) studies demonstrated the absence of any drug - polymers interaction. Promising characteristics were observed in rheological behavior and release kinetics. The size of microcapsules and percentage yield was in the range of 676 to 727 µm and 69 to 77%, respectively. Scanning electron micrographs revealed that microcapsules were discrete, spherical and free flowing. Entrapment efficiency and uniform drug release kinetics were some of the probable characteristics depicting the novel formulation design of Gliclazide microcapsules.

Pakistamide C, a new sphingolipid from Abutilon pakistanicum

The Abutilon genus from the Malvaceae family is of medicinal importance, and members of this genus are distributed in the tropical and subtropical regions of Asia and other parts of the world. Abutilon pakistanicum Jafri & Ali is mainly found in Pakistan. It has been used by different systems of traditional medicines to treat different diseases. Pakistamide C, a new sphingolipid, has been isolated from the ethyl acetate soluble fraction of the methanolic extract of A. pakistanicum. Different spectroscopic techniques such as NMR (1H, 13C, COSY, NOESY, HSQC, HMBC) and Mass spectrometry (EI-MS, and FAB-MS experiments) were used to elucidate the structure of pakistamide C.

Corniculatin A, a new flavonoidal glucoside from Oxalis corniculata

Oxalis corniculata L. (creeping wood sorrel) is medicinally important member of family Oxalidaceae, and is distributed in the tropical and subtropical regions of the world. It has been used in different systems of traditional medications for different diseases. Corniculatin A, a new flavonoid glucoside, was isolated from the ethyl acetate soluble fraction of the whole plant along with luteolin, luteolin-7-O-β-D-glucoside and β-sitosterol-3-O-β-D-glucoside, This is the first report of these compounds from this species. Their structures were elucidated on the basis of spectral data including mass and 2D NMR experiments.

Ventricular septal defect in infants and children with increased pulmonary vascular resistance and pulmonary hypertension - surgical management leaving an atrial level communication

To evaluate the surgical and medical efficacy of the patients operated for Ventricular Septal Defect [VSD] with Pulmonary Hypertension and Pulmonary Vascular Resistance [PVR]. Infants and children with elevated PVR and Pulmonary Hypertension are associated with significant mortality and morbidity after surgical closure. Circulatory assist devices and sophisticated medicines may not be available to help in the management of infants and children with elevated Pulmonary artery pressure and resistance. We left Patent Foramen Ovale [PFO] or made atrial communication to decrease the morbidity and mortality associated with the closure of large VSD in this risky group. Sixteen infants and children were operated with median age of 12 months, operated by the same surgeon [IU], from January' 2004 to December' 2005. They were with large VSD of elevated PVR [3.9+0.3] and underwent VSD closure leaving PFO or artificial ASD [5mm]. Surgical approach was through right atrium. Post operatively, all the patients were electively ventilated for 36 hours. They were given intravenous dilators [Glyceral Trinitrate + Phentolamine] and oral Sildenafil up to 1mg /Kg, six hourly. Five cases went into acute pulmonary hypertensive crisis postoperatively, and were rescued by Prostacycline Nebulization. Sixteen patients had VSD as the primary lesion that underwent operation. The overall early mortality was 6.25% [1/16]. There have been no late deaths. Closure of large VSD with elevated PVR can be performed, leaving PFO or artificial ASD, with acceptable mortality and morbidity