Distribution, geochemical behavior, and risk assessment of arsenic in different floodplain aquifers of middle Gangetic basin, India.

The present study interprets the distribution and geochemical behavior of As in groundwaters of different regions along the floodplains of Ganga river (Varanasi, Ghazipur, Ballia), Ghaghara river (Lakhimpur Kheri, Gonda, Basti), and Rapti river (Balrampur, Shrawasti) in the middle Gangetic basin, India for risk assessment (non-carcinogenic and carcinogenic). The concentration of As in groundwaters of these floodplains ranged from 0.12 to 348 µg/L (mean 24 µg/L), with around ~ 37% of groundwater samples exceeding the WHO limit of 10 µg/L in drinking water. Highest As concentration (348 µg/L) was recorded in groundwater samples from Ballia (Ganga Floodplains), where 50% of the samples had As > 10 µg/L in groundwater. In the study area, a relatively higher mean concentration was recorded in deep wells (28.5 µg/L) compared to shallow wells (20 µg/L). Most of the high As-groundwaters were associated with the high Fe, bicarbonate and low nitrate and sulfate concentrations indicating the release of As via reductive dissolution of Fe oxyhydroxides. The saturation index values of the Fe minerals such as goethite, hematite, ferrihydrite, and siderite showed the oversaturation to near equilibrium in groundwater, suggesting that these mineral phases may act as source/sink of As in the aquifers of the study area. The health risk assessment results revealed that a large number of people in the study area were prone to carcinogenic and non-carcinogenic health risks due to daily consumption of As-polluted groundwater. The highest risks were estimated for the aquifers of Ganga floodplains, as indicated by their mean HQ (41.47) and CR (0.0142) values.

The novel role of ß-aescin in attenuating CCl4-induced hepatotoxicity in rats.

CONTEXT: ß-Aescin has anti-inflammatory, anti-oxidant and antiedematous properties. OBJECTIVE: The present study investigated the hepatoprotective effect and underlying mechanisms of ß-aescin in CCl4-induced liver damage. MATERIALS AND METHODS: Thirty-five Wistar rats were divided into six groups: normal control, CCl4 control, silymarin (50 mg/kg, p.o) and ß-aescin (0.9, 1.8 and 3.6 mg/kg, i.p.) treatment for 14 d. CCl4 (1 mL/kg, i.p. for 3 d) was administered to produce hepatic damage. Ponderal changes and liver marker enzymes were estimated. Hepatic oxidative and nitrosative stress was estimated by levels of thiobarbituric acid reactive substances (TBARS), glutathione (GSH) and nitrite/nitrate. Serum TGF-ß1 and TNF-α were estimated by ELISA technique. Hepatic collagen and histopathological studies were carried out. RESULTS: ß-Aescin (3.6 mg/kg) markedly decreased CCl4-induced increased levels of ALT, AST, ALP (71.77 versus 206.7, 71.39 versus 171.82, 121.20 versus 259 IU/L, respectively), total bilirubin (0.41 versus 1.35 mg/dL), TBARS (2.0 versus 8.83 nmol MDA/mg protein), nitrite/nitrate (352.50 versus 745.15 µg/mL) and increased CCl4-induced decreased GSH levels (0.095 versus 0.048 µmol/mg protein). ß-Aescin (3.6 mg/kg) induced focal regenerative changes in liver and markedly decreased TBARS (2.0 versus 8.83 nmol MDA/mg protein), nitrite/nitrate (352.50 versus 745.15 µg/mL), TGF-ß1 (92.28 versus 152.1 pg/mL), collagen content (110.75 versus 301.74 µmol/100 mg tissue) and TNF-α (92.82 versus 170.56 pg/mL) when compared with CCl4 control. DISCUSSION AND CONCLUSION: The findings suggest that ß-aescin has a protective effect on CCl4-induced liver injury, exhibited via its anti-inflammatory, antioxidative, antinitrosative and antifibrotic properties inducing repair regeneration of liver. Hence, it can be used as a promising hepatoprotective agent.

Doxorubicin-loaded photosensitive magnetic liposomes for multi-modal cancer therapy.

Multifunctional magnetic nanosystems have attracted an enormous attention of researchers for their potential applications in cancer diagnostics and therapy. The localized nanotherapies triggered by the external stimuli, like magnetic fields and visible light, are significant in clinical applications. We report a liposomal system that aims to treat cancer by magnetic hyperthermia, photodynamic therapy and chemotherapy simultaneously. The liposomes enclose clinically used photosensitizer m-THPC (Foscan) and anti-cancer drug doxorubicin, in its hydrophobic lipid bilayers, and contains magnetite nanoparticles in hydrophilic core. Three different sizes of magnetic nanoparticles (10, 22 and 30nm) and liposomes (40, 70 and 110nm) were used in this study. Magnetite single domain nanoparticles forming the magnetic core were superparamagnetic but liposomes expressed slight coercivity and hysteresis due to the clustering of nanoparticles in the core. This enhanced the heating efficiency (specific power loss) of the liposomes under an AC field (375kHz, 170Oe). Cell viability and toxicity were studied on HeLa cells using MTT assay and proteomic analysis. Confocal and fluorescence microscopy were used to study the photosensitizer's profile and cells response to combined therapy. It revealed that combined therapy almost completely eliminated the cancer cells as opposed to the separate treatments. Magnetic hyperthermia and photodynamic therapies were almost equally effective whereas chemotherapy showed the least effect.

Protective effect of Mimosa pudica L. in an L-arginine model of acute necrotising pancreatitis in rats.

Mimosa pudica is used in traditional medicine for treating various disorders such as inflammatory conditions, diarrhoea, insomnia, alopecia, urogenital infections and wounds. The present study investigated the effect of M. pudica extract (MPE) on L-arginine-induced acute necrotising pancreatitis in rats. The ethanolic extract of M. pudica leaves was studied for the presence of quercetin and gallic acid using high-performance liquid chromatography. Four groups were employed-normal control rats, L-arginine control rats (two intraperitoneal [i.p.] injections of 2 g/kg at an interval of 1 h), MPE-treated rats (400 mg/kg orally) and melatonin-treated rats (positive control 10 mg/kg i.p.), which were further divided into subgroups according to time points (24 h, 3 days and 14 days). Serum amylase, lipase, tumour necrosis factor-α (TNF-α), pancreatic amylase, nucleic acid content, protein, transforming growth factor-ß1 (TGF-ß1), thiobarbituric reactive substances, glutathione, nitrite/nitrate, collagen content and histopathological examination were carried out. MPE significantly improved acute necrotising pancreatitis by modulating diagnostic markers of pancreatitis such as serum lipase and pancreatic amylase, inflammation (TNF-α), and oxidative and nitrosative stress. Moreover, MPE administration induced regenerative changes in the pancreas evidenced by increased levels of pancreatic proteins, nucleic acid content and histopathology report. In addition, MPE improved TGF-ß1 and collagen levels thereby preventing fibrosis. The current investigation indicates the novel role of MPE in reducing the severity of acute necrotising pancreatitis by plausible mechanisms such as anti-inflammatory and anti-fibrotic activity and by promoting repair and regeneration of the pancreas.

Clinical indications for Gallium-68 positron emission tomography imaging.

BACKGROUND: (68)Ga-PET imaging is showing slow but steady progress when compared to (18)F-FDG PET. The advantage of in-house preparation of (68)Ga without necessity of a cyclotron, and the new generator configuration with future possibility of freeze-dried kits would make it a promising PET agent for the future. METHODS: An exhaustive literature exploration was performed using the search engines High-Wire Press, Pubmed, Embase and library databases. Recent reviews on the subject and up-to-date studies on the topic were found that described the role of (68)Ga-PET imaging. Clinical experiences, including our own are described. RESULTS: Recent resurgence in development of peptides labelled with radiometals, for diagnostic and therapeutic purposes, resulted in a new beginning for (68)Ga-PET imaging. Pre-clinical experience employing animal models and investigation of tracer kinetics/tumour uptake measurements using dynamic (68)Ga-PET have provided data regarding identification of Somatostatin receptors subtypes on many tumours. Present published experiences including our own support these and highlight current clinical utility of (68)Ga-PET imaging. (68)Ga-DOTATOC and (68)Ga-DOTANOC are the most prominent radiopharmaceuticals used nowadays. CONCLUSION: (68)Ga-PET is employed in the management of neuroendocrine tumours and neural crest tumours (phaeochromocytoma and paraganglioma) with diagnostic and therapeutic implications where it compliments present radiologic and scintigraphic procedures. Diagnosis and radiotherapy treatment planning for meningiomas in pertinent clinical setting is another potential use of (68)Ga-PET. Limited studies have shown its utility in prostate cancer but further studies are contemplated. Therefore, current experience tends to open a new horizon for the clinical utility of (68)Ga-PET imaging in future.

Radioiodinated metaiodobenzylguanidine in the diagnosis and therapy of carcinoid tumors.

Carcinoid tumors account for less than 1% of all malignancies and the majority arises in the gastrointestinal system. These tumors are slow-growing compared with adenocarcinomas and they differ from the other neuroendocrine malignancies by their protean clinical presentation. Carcinoid tumors were previously considered indolent, but they can manifest malignant characteristics with metastatic spread which often results in a poor prognosis. Although there have been advances in diagnostic and treatment modalities, carcinoid tumors are still frequently diagnosed late, often when the tumor has metastasized and patients have developed carcinoid syndrome. Diagnosis, prognosis and treatment options are based on biochemical markers and imaging investigations. High concentration of urinary 5-HIAA, elevated plasma serotonin and chromogranin A levels help to establish the initial diagnosis of carcinoid tumors. In addition to the computed tomography and magnetic resonance imaging, molecular imaging modalities such as OctreoScan, metaiodobenzylguanidine (MIBG) imaging and more recently PET imaging are used in detecting the primary malignancy and metastatic involvement. Surgery is the mainstay of treatment of non-metastatic carcinoid tumors. Cytotoxic chemotherapy has limited role because of the chemoresistant nature of these tumors. Because carcinoid tumors express somatostatin receptors, somatostatin analogues, which inhibit release of serotonin and other neuroendocrine peptides, are often used, but their use is limited to symptom control. Treatment using high doses of radionuclides, such as radiolabeled somatostatin analogues and MIBG, is a more recent option, which offers a definite advantage in management. In this article, we review the current state of the art in the diagnosis and treatment of carcinoid tumors as well as the role of MIBG in their diagnosis and management.

An audit of perioperative cardiac arrests in a Southeast Asian university teaching hospital over 15 years.

An audit of the incidence, causes and outcome of perioperative cardiac arrest was conducted in a university hospital in Pakistan. All perioperative cardiac arrests from induction of anaesthesia to post anaesthesia care unit discharge or intensive care unit admission during noncardiac surgery, from January 1992 to December 2006 were included. Patients' demographic information, physical status and type of surgery and anaesthesia were noted. Outcome variables were noted as immediate survival and survival to discharge. Anaesthesia-related cardiac arrests were identified and their causes analysed. Forty-two cardiac arrests occurred among 140,384 patients. Overall frequency was 2.99 per 10,000 (95% confidence interval: 2.90 to 3.08). Twenty-four (3.77/10,000) were females. Thirty-four (13.59/10,000) patients were ASA physical status III to V, 10 (4.95/10,000) were children and 14 (4.28/10,000) above 60 years. Sixteen patients (6.48/10,000) were undergoing emergency surgery. Anaesthesia was deemed primarily responsible in nine cases (0.64/10,000). The causes of anaesthesia-related arrests were medication related (4), airway related (3), massive air embolism (1) and under-replacement of fluids (1). The event was considered to be avoidable in 26 cases. Seventeen patients died during the arrest, 15 survived more than one hour and 10 were discharged home. The number of perioperative cardiac arrests and their mortality was higher in patients with poor physical status and in emergency surgery. The number was also higher in infants, patients above 60 and females. The majority of the cases were considered avoidable, indicating the importance of prevention strategies.

Distribution of a platinum anti-tumour drug in HeLa cells by analytical electron microscopy.

The distribution of Pt in HeLa cell sections after cell treatment with cis-Pt(NH3)2Cl2 dissolved in dimethylsulphoxide was probed by analytical electron microscopy. Primary targets were the nucleolus and the inner side of the nuclear double membrane. Even after solvolysis in dimethylsulphoxide the drug reached similar sites. It is suggested that cell death may be due to Pt inhibition at the initiation sites of DNA synthesis.